Abstract:Objective To establish an improved type Ⅱ cardio-renal syndrome rat model and evaluate it. Methods　Twenty male SD rats were randomly divided into sham and model groups with 7 rats in the sham group and 13 rats in the model group. The model group received the method of squeezing the heart under a small animal anesthesia machine to permanently ligate the left anterior descending branch of the coronary artery to cause myocardial infarction. One week later, unilateral nephrectomy (right nephrectomy) was performed. The rats underwent cardiac echocardiography, pathological staining, and blood and urine tests at 6 weeks to verify model establishment. Results　Compared with the sham group, the cardiac function assessed by echocardiography and the endogenous creatinine clearance rate in the model group rats were significantly decreased (P< 0. 01), and the levels of brain natriuretic peptide, blood creatinine, urea nitrogen, and 24 h urine protein in the model group were significantly increased (P< 0. 01). HE staining revealed a disordered myocardial arrangement, glomerular atrophy, and inflammatory cell infiltration in model group rats. Picric acid- Sirius red staining showed a significant increase in myocardial collagen fibers, an irregular arrangement of renal tubules, and a large amount of collagen deposition in model group rats. The positive staining area ratio was also significantly increased (P< 0. 01). Conclusions 　This improved modeling method provided a type Ⅱ cardio-renal syndrome rat model with s simple operation, minimal surgical trauma, and low mortality rate. This model simulates the early onset of cardiac and renal function damage and pathological changes in type Ⅱ CRS, laying the foundation for systematic and in-depth research on the pathogenesis and pathological mechanism of type Ⅱ cardio-renal syndrome.

Abstract:Objective To investigate the effects of N-acetyl-D-glucosamine (GlcNAc) on acute pancreatitis in rats. Methods　Twenty male SD rats were randomly divided into a control group, AP group, low GlcNAc + AP group and high GlcNAc + AP group, with five rats in each group. Acute pancreatitis was induced in AP group, low GlcNAc + AP group and high GlcNAc + AP group by two intraperitoneal injections of 2.5 g/ kg L-arginine with a 1 hour interval. Among them, low GlcNAc + AP group and high GlcNAc + AP group were administered 50 and 200 mg/ kg GlcNAc, respectively, by intraperitoneal injection at 24 hours before the first intraperitoneal injection of L-arginine. Group control and AP were intraperitoneally injected with the same volume of normal saline. After 24 h, the rats were sacrificed, and serum and pancreatic tissues were collected. Pancreatic tissue morphology was observed by HE staining, and serum levels of amylase (AMY), lipase (LPS), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Protein expression of nuclear factor E2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), and peroxisome proliferator-activated receptor-γ (PPAR-γ) in pancreatic tissue was detected by Western Blot. Cluster of differentiation (CD)86, CD206 and macrophage markers (F4/80) were detected by immunofluorescence. Expression of CD86 and CD206 in pancreatic tissue was detected by immunohistochemistry. Results　(1) Compared with control group, AMY, LPS, IL-1β, IL-6, TNF-α, and MDA levels and pancreatic CD86 expression in AP group were significantly increased (P< 0. 05), while SOD activity, protein expression levels of NRF2, HO-1, and PPAR-γ , and pancreatic CD206 expression were significantly decreased (P<0. 05). (2) Compared with AP group, serum IL-1β, IL-6, TNF-α, MDA, and LPS and the pancreatic CD86 expression in low GlcNAc + AP group were significantly decreased (P< 0. 05). The PPAR-γ protein level in the pancreas was significantly increased (P< 0. 05). (3) Compared with AP group, serum AMY, LPS, IL-1β, IL-6, TNF-α, and MDA and pancreatic CD86 expression in high GlcNAc + AP group were significantly decreased (P< 0. 05), while serum SOD , and NRF2, HO-1, PPAR-γ,and pancreatic CD206 expression were significantly increased (P< 0. 05). (4) Compared with low GlcNAc + AP group, serum LPS, IL-1β and IL-6 in high GlcNAc + AP group were significantly decreased (P<0. 05). Pancreatic expression of HO-1, PPAR-γ, and pancreatic CD206 were significantly increased ( P< 0. 05). Conclusions 　GlcNAc treatment attenuates acute pancreatitis injury in AP rats, possibly by activating the NRF2/ HO-1 signaling pathway to inhibit oxidative stress and promoting M2 macrophage polarization to attenuate pancreatic injury in AP rats.

Abstract:Objective To establish a novel rat model of chronic skeletal muscle composite injury in the lumbar region, to explore its mechanism and treatment method in depth. Methods　Twenty-eight SD rats were randomly divided into control group (n= 10) , Hitting injury model(HIM) group (n= 9),Composite damage model(CDM) group (n= 9) (vertical blow combined with forced prolonged sitting). Open field test, HE staining and PCR sequencing were performed 3 days after modeling. Results　The open field distance of rats in HIM group was significantly shorter than that in the CDM group, and both groups had shorter distances than the control group. HE staining showed multiple muscle fiber breaks, significant widening of muscle gaps, uneven distribution of muscle nuclei, and visible congestion in the model group of simple blow injury; In the CDM group, muscle fibers were ruptured, the muscle gaps were slightly widened, and inflammatory cell infiltration was observed between the muscles, especially around the muscle fiber breakage, with muscle fiber nuclei gathering. A volcano plot of the sequencing result suggested significant differences in the Pf4 gene. GO analysis of muscle tissue in model group rats showed upregulation of oxygen binding and carrier activity pathways. Conclusions This study attempted to establish a composite skeletal muscle injury model to study the pathological changes of chronic skeletal muscle injury in the low back pain and evaluate the efficacy of treatment method. It has practical application value in animal experiments for chronic non-specific low back pain.

Abstract:Objective 　To observe the effects of plantar injection of complete Freund’s adjuvant (CFA)on paindepressive behavior and changes in hippocampal monoamine neurotransmitters in rats to establish an animal model of related comorbidity. Methods 　Sixteen male, 8-week-old, SPF-grade healthy SD rats were randomly divided into model and control groups with eight rats in each group. In the model group, rats were anesthetized and injected with 100 μL CFA in the left hind paw to induce the comorbid chronic inflammatory pain and depression model. In the control group, rats were injected with the same volume of saline. Pain thresholds were measured using the Von Frey hair and thermal radiation instrument, and depression-like behaviors were assessed using the open field test (OFT), tail suspension test (TST), and forced swim test ( FST). Enzyme-linked immunosorbent assays were used to measure 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE)in rat hippocampal tissue. Histological changes in the hippocampal area were observed by hematoxylin-eosin(HE) staining. Results 　Compared with the control group, the mechanical withdrawal threshold and thermal withdrawal latency in the model group were significantly decreased at 3, 7, and 14 days (P< 0. 01). The total distance in the OFT was significantly reduced at 7 and 14 days (P< 0. 01), and the time spent in the center zone was significantly decreased at 14 days (P< 0. 01). Immobility time in the TST was significantly increased at 14 days (P<0. 01), and the immobility time in the FST was significantly increased at 7 and 14 days(P< 0. 05, P< 0. 01). 5-HT, DA, and NE contents in hippocampal tissue of the model group rats were significantly reduced compared with those in the control group (P< 0. 01), and hippocampal tissue in the model group showed pathological changes, including irregular neuronal shapes, loose and disordered arrangement, increased intercellular space, some unclear cell nuclei, and some neuronal contraction and apoptosis. Conclusions 　Injection of 100 μL CFA into the footpad causes pain hypersensitivity, depression-like behavior, significant reductions in monoaminergic neurotransmitters in the hippocampus, and histological changes in the hippocampus, effectively simulating the manifestations of comorbid pain and depression, and is an experimental model to study the pathological mechanisms of comorbid chronic inflammatory pain and depression.

Abstract:Objective 　To investigate the causes of infertility and its pathological mechanism in female SD rats with spontaneous dwarfism (short stature rat, SSR). Methods　Adult wildtype and SSR female SD rats were used in this study. A vaginal smear was used to observe changes in the motile cycle. Ovulation promotion was compared using the simultaneous estrus supernumerary ovulation method . Ovarian and uterine weight and body weight, and ovarian and uterine indices were measured. AMH, E2, FSH, LH, and FSH/ LH levels in serum were measured. Transcriptome sequencing of ovarian tissues was performed to analyze gene expression differences. Results　No abnormalities were observed in the estrous cycle of SSR female rats. The body weight of SSR female rats was significantly lower than that of wildtype rats, and their ovarian and uterine indices were significantly higher than that of wildtype rats. The mean number of ovulations was significantly higher in wildtype rats than in SSR female infertile rats (P< 0. 001). Serum AMH (P< 0. 01) and E2 (P< 0. 05) levels were significantly higher in wildtype rats than in SSR female infertile rats, and serum levels of FSH, LH, and FSH/ LH (P<0. 05) were significantly lower in SSR infertile females than in SSR infertile rats, while PROG showed no significant difference. Transcriptome sequencing yielded 250 differentially expressed genes, including 190 upregulated and 60 downregulated genes. p53 signaling pathway and cytokine-cytokine receptor interaction. The MCC, MNC, EPC, and degree calculations of the CytoHubba plug-in were used to screen the top 10 significant nodes. The intersection was used to finally obtain nine hub genes, namely Cxcl1, Cxcl2, IL1a, IL1b, Cd80, Mmp13, Mmp8, Fgf3, and Ptgs2. Conclusions Infertility in SSR female rats may be related to a decreased ovarian reserve function and poor ovarian response. Cxcl1, Cxcl2, IL1a, IL1b, Cd80, Mmp13, Mmp8, Fgf3, and Ptgs2 were associated with infertility, laying a theoretical foundation to further explore infertility mechanisms.

Abstract:Objective 　Apply modified bilateral carotid artery ligation to establish a VD rat model to observe changes in cerebral blood flow and expression of angiogenic proteins. Methods　Thirty-six SD male rats were randomly divided into a sham group (n= 18) and model group (n= 18). In the sham group, only the bilateral carotid artery was isolated without ligation, whereas in the model group, the bilateral carotid artery was ligated to establish the VD model. The Morris water maze behavior test was applied before and 14 days after modeling. Variation in cerebral blood flow was detected by laser speckle contrast imaging. Protein expression of HIF-1α, VEGF, and HO-1 was detected by Western Blot. IL-4 and IL-10 contents were measured by ELISA. Results　At 14 days after modeling, escape latency was significantly prolonged and the frequency of crossing the platform had significantly decreased in the model group compared with the sham group (P< 0. 05). At 2 hours, 3 days, and 7 days after modeling, cerebral blood flow in the model group was significantly lower than that in the sham group (P< 0. 05). At 14 and 21 days after modeling, no significant difference was found in cerebral blood flow between sham and model groups (P> 0. 05). In the model group, cerebral blood flow was decreased to a minimum at 2 hours after modeling (P< 0. 05) and then began to recover. The peak of recovery occurred at 3 ~ 7 days after modeling and returned to the level before modeling on day 14 after modeling. At postoperative day 21, expression of HIF-1α, VEGF, and HO-1 proteins in the hippocampus of the model group was increased remarkably (P< 0. 05) and the serum contents of IL-4 and IL-10 in the model group were significantly increased compared with those in the sham group (P< 0. 05). Conclusions 　The variation in cerebral blood flow in the VD rat model established by the modified bilateral carotid artery ligation was dependent on time. At postoperative day 21, HIF-1α, VEGF, and HO-1 in the hippocampus were increased significantly, which was accompanied by increased levels of IL-4 and IL-10.

Abstract:Objective 　By summarizing experimental data of animal models of type 2 diabetes mellitus (T2DM) and its microvascular complications in rats and mice as animal models, the biochemical indexes were analyzed in order to provide theoretical reference for future experiments. Methods 　The main topics of “ type 2 diabetes” “ diabetic nephropathy” “diabetic foot” and “diabetic retinopathy” were searched on China National Knowledge Infrastructure and PubMed databases to screen out the journal literatures related to T2DM and microvascular complications in clinical and animal experiments published from October 31, 2019 to October 31, 2022. The subjects, disease types, detection indicators and other contents recorded in the literature were sorted out and summarized, and a database was established for statistical analysis. Results　A total of 510 literatures were selected, among which fasting blood glucose was the most frequently used biochemical index in T2DM experiment, urine protein level was the most frequently used biochemical index in diabetic nephropathy experiment, and serum inflammatory factors were the most frequently used biochemical index in diabetic foot and diabetic retinopathy experiment. Conclusions 　By analyzing the application frequency of biochemical indicators in T2DM and its microvascular complications, this study can provide an important reference for clinical diagnosis and treatment of the disease and the development of animal experiments.

Abstract:Objective 　To study the application of an animal model of glaucoma and provide a reference for improved animal experimental method and models. Methods　We searched the CNI and PubMed databases using the terms “glaucoma ”and “animal models” to identify studies related to animal models of glaucoma from 2012 to 2022. The study species, sex, modeling method , and detection indexes were summarized, and a database was established for statistical analysis. Results　In total, 400 articles conforming to the criteria were selected. Most of the experimental animals were C57BL/ 6J mice and most of them were male. The most common modeling method were anterior chamber injection-induced, transgenic, and laser photocoagulation-induced models. The most frequent detection indicators included intraocular pressure measurement, histopathology, Western Blot analysis, and immunohistochemistry. Conclusions 　Numerous method have been used to construct glaucoma animal models, but the intervention of related traditional Chinese medicine factors is less. It is suggested to increase the glaucoma animal model combined with disease and syndrome. This study evaluated different animal models of glaucoma by data mining to provide references for the construction of animal models with high modellingsuccess rates, good reproducibility, and high clinical coincidence, as well as providing ideas for model improvement.

Abstract:Traditional Chinese medicines have demonstrated clinical efficacy in preventing and treating chemotherapy-induced peripheral neuropathic pain (CIPNP). However, their specific clinical application and mechanism of action require further in-depth study and exploration. There is thus a need to develop more accurate and clinically relevant animal models that reflect the occurrence and development of human diseases as a tool for research. This review provides an in-depth analysis and discussion of the recent establishment and detection criteria of existing rat and mouse animal models of paclitaxel-induced peripheral neuropathic pain. We also evaluate and explain the application of these models for the prevention and treatment of CIPNP in traditional Chinese medicine, thus providing a theoretical basis and reference for future experimental and mechanistic research on the subject. This research will benefit clinical practice and promotion, offering valuable insights into preventing and treating CIPNP using traditional Chinese medicines.

Abstract:Dilated cardiomyopathy is a main disease that causes heart failure and exhibits etiological heterogeneity. Nearly a quarter of dilated cardiomyopathy in patients is related to genetics, and ventricular dilation and myocardial systolic dysfunction are the main characteristics of the disease. LMNA mutation is a major cause of hereditary dilated cardiomyopathy, and arrhythmia is a major clinical manifestation of hereditary dilated cardiomyopathy with LMNA mutation. In recent years, establishment of a dilated cardiomyopathy model in C57/ B6 mice and its treatment by focused gene therapy has been a research focus, and some important conclusion have been drawn from the establishment of large animal models in dogs and pigs. However, large animals, especially non-human primates, are closer to humans. At present, dilated cardiomyopathy is not involved in the heart disease model of non-human primates. Therefore, this article reviews studies on rodent and large animal models of dilated cardiomyopathy at the genetic level and proposes the idea of developing a dilated cardiomyopathy model in a non-human primate. It also provides new ideas to study the pathogenesis and clinical treatment.

Abstract:Ketogenic diet can supplement blood ketone, provide energy for skeletal muscle, and affect the athletic performance and recovery of animals and humans after fatigue. In this paper, it was found that ketogenic diet transformed muscle fibers from Ⅱb to Ⅱa through axonal germination and nerve reinnervation, improved the quality and function of mitochondria of fast muscle and increased histone acetyltransferase to enhance skeletal muscle strength. Using ketone body to provide energy, it can reduce glycolysis and improve the ability of fatty acid oxidation in slow muscle to improve exercise endurance; It can reduce endoplasmic reticulum stress, oxidative stress and inflammatory reaction of skeletal muscle, protect the body from injury, reduce the consumption of muscle glycogen and the accumulation of lactic acid, reduce fatigue after exercise and promote recovery. It is considered that ketogenic diet has low negative effects on the body, can improve sports performance and accelerate fatigue recovery, and can be used as a diet scheme in competitive sports and rehabilitation training.

Abstract:Natural killer (NK) cells as intrinsic immune cells kill tumor cells without the need for pre-stimulation by tumor antigens. Therefore, NK cell based immunotherapy has unique advantages and has made significant progress in tumor treatment. In this article, we review the development, classification, and mechanism of NK cells as well as the applications of NK cell based immunotherapies, including immune checkpoint inhibitors, adoptive cell therapy, and NK cell adapters in tumor immunity. Thus, we elucidate the principle, current status, and developmental trend of NK cellbased anti-tumor immunotherapies to provide ideas for their development and application in the field of tumor immunotherapy.

Abstract:As endogenous chemical substances, neurotransmitters play a vital role in maintaining normal life activities. Abnormal levels of neurotransmitters can lead to physical, mental, and some neurodegenerative diseases. However, the ultralow concentration, complex chemical properties, and release modes of neurotransmitters make their accurate detection in vivo a great challenge. To accurately monitor neurotransmitters in the brain and accurately understand the release kinetics of neurotransmitters, we reviewed several method commonly used in the past five years to detect neurotransmitters in vivo and their research progress. The basic principle and applicability of microdialysis, electrochemical sensors, and fluorescence sensors are introduced in detail.

Abstract:As the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic continues to spread globally, its genome is undergoing mutations and evolution, giving rise to various strains such as α, β, γ, and δ. Therefore, the continuous development of drugs and vaccines targeting the various strains has become pivotal to addressing the COVID-19 pandemic. Establishing animal models of SARS-CoV-2 enables study of the pathogenesis of the virus and is crucial for evaluating the efficacy of drugs and vaccines against SARS-CoV-2. However, commonly used animal models such as mice exhibit limited susceptibility to wildtype SARS-CoV-2 infection, underscoring the urgent need for animal models that can be infected with the novel coronavirus and better simulate the human pathological and physiological conditions. This review summarizes the animal models used to study SARS-CoV-2 infection and transmission, and their progress in characterizing the viral immunopathology.

Abstract:In recent years, cortisol has been used as a biomarker to assess stress in dogs. To evaluate the welfare of dogs, we reviewed cortisol levels and changes in dogs under various stresses. We explored the influential factors that relieve stress in accordance with variations in cortisol levels, to improve the measures which reduce stress in dogs. It is recommended to apply cortisol measurement and behavioral observation comprehensively to evaluate stress in dogs more accurately.

Abstract:Rat is one of representative laboratory animals since the genetic and the environment is comparatively easy to control. Laboratory rats are widely used in the area of physiology, neuroethology, pathology and toxicology due to the approximately ten times larger body size compared to mouse, offering several unique advantages in surgical procedures and clinical sampling of blood, tissues, etc. This paper reviews the cultivation and utilization history of the laboratory rat resources abroad such as strain breeding, preservation and database establishment to provide references for collecting, sharing and utilizing laboratory rat resources in our country.