Abstract:Objective To establish a porcine allogeneic left lung orthotopic transplantation model to closely simulate human lung transplantation. Methods Twelve Huanjiang mini-pigs were used as donors and 12 Bama mini-pigs as recipients. The left lung orthotopic transplantation was completed by the left fourth intercostal thoracotomy. At 1 h, 2 h, 4 h, 6 h, 12 h after transplantation, the left and right pulmonary artery pressure were measured, the left and right pulmonary vein blood gas was analyzed, and samples of the left and right lung tissues were taken to determine the water content and for pathological examination. Results All animals survived, and the transplanted pulmonary vein blood PaO₂/FiO₂ and PAP were rised along with the prolonged postoperative time, compared with those of the recipient normal lung showing a significant difference (P<0.05). With the pass of time, there were increasing edema, inflammatory cell infiltration, RBC ooze, thickening of alveolar wall in the transplanted lung tissue, and some alveolar lumen occlusion and lung tissue consolidation. The water content of the transplanted lung tissue was increased significantly compared with that in the recipient lung tissue (P<0.05). Conclusions The established method in this study provides an ideal animal model for research on lung transplantation ischemia-reperfusion injury and immune rejection mechanism.

Abstract:Objective To investigate the lung transplantation by establishing an orthotopic mouse lung transplantation model by microsurgery. Methods Thirty SPF male C57BL/6 mice served as both recipient and donor. Orthotopic lung transplantation models were established in the mice by three-cuff anastomotic technique. Native and transplanted lung tissue samples were taken at 7, 14, 21 and 28 days after transplantation for pathological evaluation of the outcomes using HE staining. Results After learning curve, 30 mice received transplantation. All mice survived and the success rate of lung transplantation was 89%. The donor operation time was 35.2±9.81 min and recipient operation time was 24.6±7.42 min. Mean cold ischemia time was 46.6±8.92 min, and warm ischemia time was 17.2±3.08 min. No histological alterations were routinely detected in the isograft lungs at all times post-transplantation compared with the native lungs. Conclusions Mouse lung transplantation model can be successfully established by the established technique with a high success rate and excellent reproducibility, and is in accordance with the physiology of clinical orthotopic lung transplantation. It is a good animal model for studying the pathogenesis and treatment of lung transplantation.

Abstract:Objective To modify the techniques for establishment of an abdominal working heart transplantation model in rats and to sum up the key factors to success. Methods A total of 180 12-week old Brown Norway rats (donor) and Lewis rats (recipient) were used in this study: 50 BN rats and 50 Lewis rats for pilot experiment, and 40 BN rats and 50 Lewis rats for the formal experiment. The rat model of working heart heterotopic transplantation was adopted and established by Wiedemann's mode. We transplanted the heart from BN rats to Lewis rats and analyzed the survival rate, causes of death and histological changes of the heart (HE staining) in this experiment. Results After exercise and modification, the survival rate was increased to 77.5%, and the mean total duration of operation was 71±11 min, and the mean ischemic time of the donor hearts was 34±5 min. Histological examination (HE staining) of the cardiac allograft showed a mild inflammatory cell infiltration in the graft at 24 h after transplantation, indicating that the model was reliable. Conclusions A variety of factors may affect the final operation success rate in the establishment of this heart transplantation model. Among them, the major affecting factors include: healthy animals, donor heart protection, rapid and effective vascular suture, and postoperative animal management.

Abstract:Objective To establish a large animal (sheep) model to serve the experiments of domestic pulsatile ventricular assist device. Methods Three small-tail Han-sheep were anesthetized and the vein access and artery access were achieved. The cardiopulmonary bypass was established through left thoracotomy. Ventricular fibrillation was induced. An hole was made in the apex of left ventricle and the apex cannulation was sutured to it. The aortic cannulation was sutured to the descending aorta. The two cannulations were connected to the domestic pulsatile ventricular assist device (DPVAD) and the driver was turned on. The working of DPVAD and the conditions of the animals were observed. Results The DPVAD worked well and uni-directional blood flow was driven by positive and negative pressure. The left ventricle was unloaded and the blood pressure was raised up. Conclusion The establishment of sheep model of pulsatile ventrieular assist device may play important role for the research and development of DPVAD in our country.

Abstract:Objective To establish a New Zealand rabbit model of heart failure by aortic regurgitation. Methods Adapting catheterization-induced aortic regurgitation to establish a volume overloat rabbit model of heart failure. The SBP, LVSP, LVDP, LV+dp/dt and LV±dp/dt were observed before and after modeling. The successful criteria of heart failure: the LV±dp/dtmax was decreased more than 40% and the LVDP increased more than 40%, or the LV±dp/dtmax fell down to less than 40% and the DBP should be decrease more than 40%. Evaluating the model by observing the coat color, mental status, physical activity, calculating the feed consumption index, weight gain index, heart rate, respiration frequency and other indicators.The activity of serum SOD and MDA concentration were assayed to determine the antioxidant capacity of the model animals. Enzyme-linked immunosorbent assay kit was used to detect the serum cAMP and cGMP concentration. Gene chip technology was used to analyze the difference of gene expression. Results After modeling, the hemodynamic index of SBP, DBP and LVSP were significantly decreased, LVDP was significantly decreased, LVDP was significantly increased and the LV+dp/dt and LV±dp/dt were significantly decreased. Compared with the normal control group, the model animals showed coat withered, less movement, less eating, unresponsiveness, listlessness, and reduced grab resistance after modeling. The respiratory rate of the model group was significantly increased, and this trend was increased over time. The serum SOD activity was lower, MDA concentration was higher, cAMP concentration was lower, and cGMP concentration was higher in the model group. 665 differentially expressed genes were detected. Compared with the human gene sequences, 16 characteristic genes were obtained. In these 16 genes, which were closely related to heart function, were mainly related to ion channels, muscle contraction, and signal transduction function. Conclusions This reported method to establish rabbit model of heart failure by using aortic regurgitation is reliable. The aortic regurgitation increases cardiac preload, than leads to an increase of the left ventricular end-diastolic volume, and finally results in left ventricular hypertrophy and heart failure. The results of myocardial tissue gene chip test show that there are some changes in gene expression of the model rabbits.

Abstract:Objective To study the role of endoplasmic reticulum stress and related inflammation in the kidneys of rats with diabetic nephropathy and the effect of valsartan on these lesions. Methods The diabetic rat model was induced by intraperitoneal injection of streptozotocin. Thirty-four healthy male SD rats were randomly divided into normal control group (n=10), diabetic group (n=12), and valsartan group (n=12). Valsartan (10 mg/kg) was administered daily by gavage from the next day of the diabetes induction for 6 weeks. The expression and distribution of ERS-related proteins P-IRE1α, P-JNK, and MCP-1 were examined by immunohistochemistry and Western blot. Real-time fluorescence quantitative PCR was used to detect the mRNA expressions of IRE1α, JNK and MCP-1. The 24-hour urine protein excretion, Scr, and BUN were checked.Results Compared with the control group, infiltration of inflammatory cells was aggravated in the kidneys of DM+V group, the expressions of P-IRE1α,IRE1α,P-JNK,MCP-1 were significantly increased, and the levels of IRE1mRNA and MCP-1mRNA increased compared with the DM group, infiltration of inflammation cells was alleviated in the kidney of DM+V group, the protein expressions of P-IRE1α,IRE1α,P-JNK,MCP-1 were significantly reduced, the levels of IRE1mRNA and MCP-1mRNA were reduced. While there was no significant difference in the expression of JNK mRNA and protions among the three groups. Conclusions ERS and related inflammation are activated in the kidney of diabetic rats. Inhibition of the IRE1/JNK/MCP-1 pathway of ERS and related inflammation might be responsible for the protective effects of valsartan on the kidneys of diabetic rats.

Abstract:

Abstract:Objective To detect the levels of IL-1, IL-6,TNF-α and IFN-γ in serum and colon tissue of rat models of ulcerative colitis with spleen and kidney Yang deficiency, and to explore their roles in the pathogenesis of ulcerative colitis (UC). Methods The rat model of ulcerative colitis with Yang deficiency of spleen and kidney was induced by perfusion of rhubarb decoction plus intramuscular injection of hydrocortisone and combined with TNBS (2,4,6-trinitrobenzenesulfonic acid) and ethanol enema. Sixty SPF wistar rats (body weight 180±10 g, male:female=1:1) were randomly divided into blank control group, UC model with spleen kidney Yang deficiency for 7 days, 14 days and 21 days groups, respectively. The levels of IL-1, IL-6, TNF-α and IFN-γ in serum and colon tissue were detected by ELISA. Results Compared with the blank group, the levels of IL-1, IL-6, TNF-α and IFN-γ in serum and colon tissue of rat UC model group with spleen kidney Yang deficiency were greatly increased (P<0.05), especially evidently increased in the model group at 21 days. Conclusions The pro-inflammatory cytokines IL-1, IL-6, TNF-α and IFN-γ play an important role in the pathogenesis of ulcerative colitis with syndrome of spleen and kidney Yang deficiency.

Abstract:Objective To establish a reproducible rat model of acute rectal mucosal injury induced by acetic acid. Methods Fifteen healthy Sprague-Dawley rats were randomly divided into the control group (3 rats) and experimental group (12 rats). Acute rectal mucosal injury was induced by 4% acetic acid using a cotton swab inserted into the rat rectum for 1 min to a depth of 3 cm. The morphological characteristics were analyzed by the naked eye and histology at 0.5 h and 1, 4, and 6 days after acetic acid intervention. Results All rats survived 6-day study period. The successful rate of model establishment was 100%. From 0.5 h to 1st day after acetic acid intervention, the gross morphology of recta showed congestion, edema and ulcer to ulcer complicated with hemorrhage. The histology showed necrosis and hemorrhage of the epithelial tissue of the mucosa to complete and extensive necrosis of the mucosa. The glandular structure showed partial to complete loss. The submucosa showed edema to edema complicated with hemorrhage and congestion. The interstitial tissues showed vasodilatation and congestion to inflammatory cell invasion.From 4 to 6 days after acetic acid intervention, the rectal mucosal changes were obviously improved. Epithelial and glandular regeneration and inflammatory granulation occurred, but not fully recovered, some edema and redness, partial lack of glands were still present. Conclusions 4% acetic acid for 1 min can be used to successfully induce rat model of acute rectal mucosal injury. This procedure is easy to operate, with a high success rate, reproducible, and the alterations are lasting more than 6 days. This animal model is very suitable for rapid screening of topical drugs for the treatment for rectal mucosal injury.

Abstract:Objective To study the chronic toxicity and its severity of a Chinese medicine, Anshen Bunao Liquid (ABL), in rats, provide the target organs and extent of reversibility of their adverse effects, determine its non-toxic dose, and to evaluate the safety of medication and provide reference for clinical trial dose and observation indexes. Methods Two hundred and forty healthy 6-week old Wistar rats (male:female=1:1) were divided into low, middle, and high dose Anshen Bunao liquid groups (2.5, 5, 10 mL/kg), and solvent control group (distilled water 2 mL/100 g), with 60 rats in each group. The drug was orally administered to rats once a day and 6 days per week for 26 weeks. The general state, body mass and food intake were measured.By the end of 13 weeks, 26 weeks of experiment and 4-week recovery period after drug withdrawal, hematological and biochemical indexes were assayed, organ coefficients were determined, and histopathological observation was performed. Results Long-term continuous oral administration of Anshen Bunao liquid, the general state, behavior and gross appearance showed no significant abnormal changes. Compared with the control group, no significant differences in all checked items were found in the treatment groups.During 3 and 6 months, the size and location of organs, organ weight and organ coefficient had no obvious changes, with only non-significant increase of weight of some organs. All the organ coefficients of the animals in different groups were within normal range. Histopathology showed no obvious pathological and toxicological changes even in the high-dose drug treatment group, and no delayed toxicity occurred after withdrawal of drug administration. Conclusions The Chinese drug, Anshen Bunao liquid has no obvious toxicity and no delayed toxicity after withdrawal of the drug in rats. It is expected that the planned dose in clinical use is a safe dose.

Abstract:Objective To construct rCB1 gene eukaryotic expression vector, detect its expression in the cell, and explore its influence on apoptosis in human cervical cancer CaSki cells. Methods The total RNA was extracted from rat brains. The rCB1gene was amplified by RT-PCR. The pcDNA3.1(+)-rCB1 was constructed by enzyme digestion, purification, bind the PCR purification products and pcDNA3.1 (+) DNA. The pcDNA3.1 (+)-rCB1 plasmid was transfected into HEK293 and CaSki cells by liposomes. The expression and localization of rCB1 were detected by Western blot and immunofluorescence combined with confocal laser scanning microscopy. The apoptosis rate of CaSki cells was detected by flow cytometry. The expression of rCB1, Bcl-2, Bax and Bad was detected by Western blot and real-time fluorescence quantitative RT-PCR (qRT-PCR). Results The 5300 bp pcDNA3.1(+) and 1500 bp rCB1 were obtained after digesting the pcDNA3.1(+)-rCB1. The result of sequencing was in agreement with the sequence of rCB1 gene (NM_012784.4). The rCB1 expressed in the membrane and cytoplasm when pcDNA3.1 (+)-rCB1 plasmid was transfected into HEK293 cells. The apoptosis rate of rCB1 group was increased compared with the blank group when pcDNA3.1 (+)-rCB1 plasmid was transfected into CaSki cells (P<0.05). Compared with the blank group, rCB1 gene upregulated the expression of Bax and Bad, and suppressed the expression of Bcl-2. The statistical difference was significant (P<0.05). Conclusions The pCDNA3.1(+)-rCB1 eukaryotic expression vector is constructed successfully. It is found that rCB1 is expressed in membrane and cytoplasm of HEK293 cells. rCB1 can significantly promote the apoptosis in cervical cancer CaSki cells by up-regulating the expression of Bax and Bad, and down-regulating the expression of Bcl-2 as well.

Abstract:Objective To establish a Goto-Kakizaki (GK) rat model of duodenal-jejunal bypass(DJB) and observe the changes in insulin-resistance after surgery, and to explore the mechanism of DJB surgery in treatment of type 2 diabetes mellitus. Methods Male Goto-kakizaki diabetic rats(GK, n=36)were used as experiment group and 18 healthy male Wistar rats as blank group. GK rats were randomly divided into two groups: diabetic control group and DJB surgery group (n=18). Euglycemic-hyperinsulinemic clamp technique was performed in 6 rats randomly taken from each group at third week, sixth week and ninth week after surgery, respectively. The expression levels of Gck, G6P, PEPCK mRNA in the liver and GLUT4 content on skeletal muscle cell plasma membrance were detected one week after the clamp test. Results In the DJB surgery group at the end of third week and sixth week after surgery, the levels of glucose infusion rates and the expression levels of Gck, G6P, PEPCK mRNA in the liver showed no statistically significant difference as compared with the diabetic control group (P>0.05). In the DJB surgery group at the end of 9th week after surgery, the glucose infusion rate and expression level of Gck mRNA in the liver were significantly higher, and the expression of G6P and PEPCK mRNA was significantly lower than those in the diabetic control group (P<0.05 for all). At the three time points (3rd week, 6th week and 9th week after surgery), there was no significant difference in the GLUT4 content on skeletal muscle cell plasma membrane between the diabetic control group and DJB surgery group (P>0.05 for all). Conclusions Our results indicate that the mechanism of DJB surgery improving blood glucose level may be closely related to the amelioration of insulin-resistance in the liver, thereby augmenting glucose uptake and inhibiting gluconeogenesis in liver through the regulation of glucose metabolism-related enzymes. There is no significant improvement in insulin-resistance in the skeletal muscles during the experiment period. This result implies that the effect of DJB surgery on type 2 diabetes is related to the duration of therapy.

Abstract:Objective To investigate the expression changes of macrophage migration inhibitory factor(MIF)and C-Jun N-terminal kinase (JNK) in the liver of rat with abnormal glucose metabolism and explore the pathological mechanism of abnormal glucose metabolism with non-alcoholic fatty liver disease (NAFLD). Methods Sixty SD rats were randomly divided into impaired glucose tolerance (IGT) model group (n=20), type 2 diabetes mellitus (T2DM) model group (n=20), IGT control group (n=10) and T2DM control group (n=10). IGT models were produced by feeding high-fat diet, T2DM models were produced by feeding high-fat diet for 4 weeks and intraperitoneally injected streptozotocin. Liver cell apoptosis was detected by TUNEL staining. The expression of MIF mRNA in liver tissue was determined by real-time PCR. The expressions of MIF, caspase-3, JNK proteins and phosphorylated JNK(p-JNK)in the liver tissue were determined by Western blotting. Results Apoptotic cells were obviously increased in the IGT and T2DM groups. Expression of MIF mRNA in the IGT and T2DM groups was markedly higher than that in the control group, respectively (P<0.01). The expressions of MIF, caspase-3, JNK proteins and phosphorylated JNK were markedly higher than that of the control group, respectively (P<0.05 or P<0.01). The expressions of MIF, caspase-3, JNK proteins in the T2DM group were significantly decreased compared with those of the IGT group, while the expression of phosphorylated JNK was significantly higher (P<0.01). Conclusions Abnormal glucose metabolism accompanied with NAFLD is probably related to the increase of MIF, Caspase-3, JNK and phosphorylated JNK expression.

Abstract:Objective To analyze the expression characteristics of SRPK2 (serine/arginine-rich protein specific kinase 2 mRNA and its encoded protein products in mouse testis, and to reveal its molecular role during spermatogenesis. Methods Using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting to analyze the expression of SRPK2 mRNA and its protein products in several mouse tissues. The stage-specific expression pattern of SRPK2 mRNA in mouse testis was examined by real-time quantitative PCR. Immunohistochemical staining was applied to identify the SRPK2 protein distribution in mouse testicular seminiferous tubules and indirect immunofluorescence staining was used to detect the subcellular localization of SRPK2 protein in spermatic cells. Results Semi-quantitative RT-PCR and Western blotting analysis revealed that SRPK2 was highly expressed in mice testis. Real-time quantitative PCR analysis showed that SRPK2 mRNA was expressed abundantly at the stage of 5-and 8-week old mouse testes, suggesting that SRPK2 gene has stage-specific expression patterns during mouse spermatogenesis. Immunohistochemical and indirect immunofluorescence staining demonstrated that SRPK2 protein was located around the surface of elongated sperm nucleus. Conclusions SRPK2 is highly expressed in mouse testis and has significant stage-specific expression characteristics with distinct nuclear localization. These results indicate that SRPK2 may participate in precursor mRNA splicing during mouse spermiogenesis. The molecular mechanism of SRPK2 is yet to be further studied.

Abstract:Objective To explore the establishment of a rat model of acute radiation-induced liver injury and significance of the dynamic changes of TGF-β1 expression. Methods Forty healthy 6-week old male SD rats were randomly divided into model group (n=30) and control group (n=10). The right liver of rats in the model group was given a single dose of 25 Gy 6 MV X-ray irradiation. Histopathological examination using HE staining and transmission electron microscopy were conducted to observe the liver pathological changes in rats at 3, 5, and 10 days after irradiation, serum TGF-β1 was detected, and relevant indicators of liver function (ALT, AST, ALP) were determined. Statistical analysis was performed using SPSS 17.0 software. Results At 3, 5 and 10 days after irradiation, early pathological changes in the liver cells were observed by electron microscopy, the expression of TGF-β1 was gradually increased with the time prolongation, and significant differences were found between the model group and the control group at different time points (P<0.05). The light microscopic observation of liver tissues did not show significant differences between the control group and model group. The liver ALT, AST, ALP at different time points did not show significant differences between the two groups (P>0.05). Conclusion Electron microscopy can be used to evaluate the early changes of radiation-induced liver injury, prior to the alterations visible by routine light microscopy. TGF-β1 can be used to predict the degree of radiation-induced liver injury, and may be used as a sensitive serum cytokine in predicting the degree of radiation-induced acute liver injury.

Abstract:Objective By comparing the biological characteristics among Lewis lung cancer cells (LLC), LLC orthotopic transplantation derivative cells (R1-LLC) and R1-LLC orthotopic transplantation derivative cells (R2-LLC), we evaluate their invasion and metastatic abilities in orthotopic transplantation models. Methods In vitro, we applied CCK8, clonogenic assay, and Transwell invasion assay to detect the proliferation ability, invasion ability and morphologic structures of LLC,R1-LLC, R2-LLC cells respectively, meanwhile observing morphologic structures by transmission electron microscopy. In vivo, we constructed LLC, R1-LLC and R2-LLC orthotopic transplantation models. Herein, we observed their tumor growth and metastasis. The tumor formation rate and tumor-forming time were recorded for statistic analysis. Results In vitro: LLC, R1-LLC and R2-LLC cells showed no significant difference in proliferation ability(P> 0.05), but significant differences in invasion ability: R2-LLC> R1-LLC> LLC(P<0.05). In vivo: In the orthotopic group, the tumor formation rates of LLC, R1-LLC and R2-LLC cells were 66.67%、80%、93.33%(P <0.05). Conclusions In orthotopic implantation mouse models, R2-LLC cells present higher invasion and metastatic ability than R2-LLC and LLC cells.

Abstract:Objective To investigate the potential of chronic myeloid leukemia (CML) cell line KCL22 in inducing leukemia in NOD-SCID mice for setting up a basis for constructing a CML mouse transplantation tumor model. Methods 2×10⁷ KCL22 cells in logarithmic growth phase were injected via the tail vein into experimental NOD-SCID mice whereas PBS was injected to the mice of control group. General condition of the mice of both groups was observed. Wright staining was used to observe the changes of blood and bone marrow smears. PCR was conducted to detect the transcription level of BCR-ABL, and histology with HE staining was used to evaluate the tumor cell invasion in the liver and spleen. Results Four weeks after the injection of KCL22 cells, the mice in experimental group showed physical signs of decreased reactivity, depression, swollen hindlimb muscles and petechia on the hindlimb femur. Peripheral white blood cells (WBC) began to increase after 5 weeks, with a significantly increased quantity compared with the control group (P<0.05). Immature granulocytes could be seen in blood and bone marrow smears, and tumor cell infiltration was found in the liver and spleen. BCR-ABL was highly expressed in bone marrow cells. Survival time of the experimental mice without therapy was 70 days, significantly shorter than that in the control group (>90 days) (P<0.05). Conclusions A NOD-SCID mouse model of CML transplantation tumor is successfully established with leukemia KCL22 cells.

Abstract:Objective The ECG lead II characteristics of Beagle dog, rhesus monkey, Japanese white rabbit and tree shrew were analyzed and summarized to provide reference for drug safety evaluation studies. Methods The ECG lead II of healthy adult Beagle dog, rhesus monkey, Japanese white rabbit and tree shrew were recorded to determine the interval of P, PR, QT (QTc), the QRS waves and amplitude of P, R, T waves and the ST shift. Results and Conclusion All the animals had sinus rhythm. All the four species of animals had similar ECG pattern with no particular specific changes, but had some differences of the QRS wave group and T wave. The amplitude of P and T waves in Japanese white rabbit was smaller, and the heart rate of tree shrew was faster than that of the other species of animals.The ECG lead Ⅱ database of the Beagle dog, rhesus monkey, Japanese white rabbit and tree shrew is established.

Abstract:The most important cause of late mortality after lung transplantation is obliterative bronchiolitis (OB). It is clear that a good animal model is indispensable to further unravel and clarify the pathogenesis of bronchiolitis obliterans syndrome (BOS). Many animal models have been developed to study BOS, however, so far, none of these models truly mimics the human condition. In recent years mouse models of orthotopic lung transplantation have been established, which provide potential possibilities for further studies of OB/BOS after lung transplantation. The aim of this article was to review the pros and cons of those animal models, and discuss the possible approaches to establish animal models of chronic rejection after lung transplantation.

Abstract:Atrial fibrillation (AF) is an abnormal heart rhythm characterised by rapid and irregular beating. It is caused by multiple factors and can lead to ischemia-associated thrombosis, heart failure and other complex symptoms. Based on the etiology and characteristics of AF, animal models have 3 main categories including electrical, neurohormonal or vessel-related, and structural remodeling models. New technologies such as microRNA knock-down/overexpression or CRISPR-Cas9 gene editing provide tools for constructing animal AF models and directions in the development of AF therapeutic strategies. Currently these strategies have largely focused on the cellular and molecular therapeutics rather than traditional invasive electrophysiological methods or antiarrhythmic drugs. With the aid of new tools, progress has been greatly made in a broad range of therapeutic research areas including molecular mechanisms, drug targeting and screening. This review summarizes the animal models of atrial fibrillation currently used in studies of the molecular and cellular therapeutics and notes their contributions to this research area.

Abstract:Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized by resting tremor, muscular rigidity, akinesia and postural reflex impairment. Behavioral tests of PD in animal models are essential for understanding the pathogenesis of PD as well as for the development and testing of potential therapeutics. Here we mainly use the 6-hydroxydopamine (6-OHDA)-induced rat model, to introduce a review on the research progress in non-drug-induced behavioral tests of motor function in PD rats.

Abstract:Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Currently, the combination of surgical resection and chemotherapy is the main method of treatment for OS in the clinic. Although, the survival rate has been greatly improved in OS patients with localized disease, the 5-year survival rate has remained <20%. It is very important to understand the cause of disease, to develop novel drugs or therapeutics, and to learn the disease through animal models. This review will introduce the progress of animal models of osteosarcoma over the last years.