Abstract:Objective To observe the effects of angiotensin Ⅱ(Ang Ⅱ)blockade on renal function, renal blood flow and renal oxygen consumption in chronic renal failure (CRF) rats induced by 5/6th kidney ablation /infarction (5/6A/I). Methods Sprague-Dawley rats were randomly divided into 3 groups: the normal group (group A, n =14), model group (group B, n=14) and angiotensin II blockade (Cozaar with Monopril) treatment group (group C, n =14). The chronic renal failure (CRF) rat models were induced by 5/6th kidney ablation/infarction. The tail artery systolic pressure (SBP), diastolic blood pressure (DBP) and tail vein serum creatinine (Scr), blood urea nitrogen (BUN), hemoglobin (Hb) and creatinine clearance rate (Ccr) were assessed before and after intervention. The course of treatment was sixty days. The renal blood flow (RBF), blood gas analysis of abdominal aortic and renal vein, left renal vein pressure (RVpO₂) were detected and remnant renal oxygen consumption (QO₂ /T_Na) was calculated, and the pathological changes of remnant kidney were observed after the 60 d intervention. Results (1) Compared with the group A, the levels of Scr, BUN and tail artery SBP, DBP were significantly increased (P<0.01 for all), and the levels of Ccr and Hb were significantly decreased (P<0.01) in the groups B and C, demonstrating the successful modeling. (2) Compared with the group B, the levels of Scr, tail artery SBP, DBP and QO₂/T_Na were significantly decreased (P<0.01 for all), the levels of BUN were decreased (P<0.05), the levels of Hb, Ccr and RVpO₂ were significantly increased (P<0.01 for all), the level of RBF was increased (P<0.05) in the group C after intervention.(3) The histopathological examination of the remnant renal tissue showed that the pathological changes in the group C were apparently reduced, better than those of the Group B. Conclusions Angiotensin II blockade can increase RBF, reduce renal oxygen consumption, improve renal function, and reduce the renal pathological changes in CRF rats. The mechanism of renal protection may be related to the regulation of cellular energy metabolism and improvement of renal oxygen consumption.

Abstract:Objective To explore the dynamic responses of Sertoli cells to depletion of spermatogonial stem cells by busulfan. Methods After intraperitoneal injection of 15, 30 or 44 mg/kg busulfan to mice, the spermatogenesis and the expression of GDNF, PLZF, Nanog and GFRɑ1 mRNA were assessed by real-time quantitative PCR at 5 and 28 days after the busulfan treatment. Results Glial cell line-derived neutrophic factor(GDNF) was significantly increased and showed a dose-dependent trend at 5 days after busulfan treatment, but no significant difference was seen in the expression of promyelocytic leukemia zinc finger(PLZF) and GDNF family receptor α-1(GFRα1). The testicular histology also appeared no significant difference at 5 days after busulfan treatment. At 28 days after busulfan treatment, the relative expression levels of GDNF, PLZF, Nanog and GFRɑ1 mRNA were drastically increased. Morphological observation showed that spermatogenesis damages became even more severe as the busulfan dose increased. Conclusions Sertoli cell response to the depletion of spermatogonia occurs as early as the fifth day after busulfan treatment. Production of GDNF in Sertoli cells shows a compensatory increase, which may stimulate spermatogonial stem cells to accelerate their self-renewal, reflected by the enhancing expression of Nanog and PLZF, and ultimately promote the restoration of spermatogenesis.

Abstract:Objective TALE-TFs were adopted to provide a new way in detection of the expression result of β-casein gene promoter-interesting gene expression cassettes in mouse fibroblasts. Methods TALE-TFs of eukaryotic expression plasmid and expression cassette with β-casein gene promoter and red fluorescent protein reporter gene were co-nucleofected into mouse fibroblasts by Amaxa nucleofector. Results and Conclusion β-casein gene promoter was activated by artificial TALE-TFs in the mouse fibroblasts. The way is a new expression verification system instead of mammary epithelial cells with fibroblasts.

Abstract:Objective To explore the effect of caspase-9 inhibitor on low fetal bovine serum (FBS)-induced apoptosis in cartilage endplate chondrocytes in SD rat vertebrae. Methods Disc cartilage endplates were obtained from 3-month old SD rats and subjected to sequential digestion to harvest chondrocytes for primary culture, and apoptosis was induced by 1% FBS for 48 hours. Three groups of chondrocytes were treated by 1% FBS, caspase-9 inhibitor (Z-LEHD-FMK) and DMSO, respectively. After 48 hours, apoptosis was detected by DAPI staining and flow cytometry. The expression of procaspase-9, active caspase-9 and active caspase-3 was monitored by Western blot. Results Compared with the 1% FBS group (40.8±0.84)% and DMSO group (40.2±1.56)%, the apoptosis rate of the caspase-9 inhibitor group (26.3±2.56)% was significantly lower (P<0.05). The expressions of active caspase-9 and active caspase-3 in the caspase-9 inhibitor group were significantly lower than those in the other two groups (P<0.05). Conclusions Caspase-9 inhibitor can inhibit low FBS-induced apoptosis in cartilage endplate chondrocytes of rat vertebrae, and might become a new drug for the treatment of disc degeneration.

Abstract:Objective To compare the differences of lung pathological changes of acute lung injury in mice induced by lipopolysaccharide (LPS) and graphite particles, and to explore the possible mechanisms of acute lung injury induced by fine particles of different origins. Methods 140 male specific-pathogen-free Kunming mice weighing 18-20 g were randomly divided into 7 experimental groups, in addition to the normal control group. The experimental groups were treated by intratracheal instillation of LPS solution or graphite powder suspension in different doses, respectively, to induce acute lung injury in the mice. The mortality of the mice was observed, and pathological changes of the lung tissues were examined by light and transmission electron microscopy. Western blot was used to detect the protein expression of neutrophil elastase (NE) in lung tissues , and real-time quantitative PCR was used to detect mRNA expression of monocyte chemotactic protein-1 (MCP-1)in the lung tissue . Results Compared with the normal control group, some pathological changes were observed in the lung tissues of the groups L (LPS) and G (graphite). There were numerous macrophages in the lung tissues in the group G mice, and exudate, mainly neutrophils, in the lung tissues of the group L. The NE protein expression in the lung tissue was significantly higher than that of the normal control group (P<0.05), and there was also a significant difference between the groups L and G (P<0.05). The MCP-1 mRNA expression in lung tissues was higher in the control group (P<0.01), and there was also a significant difference between the groups L and G (P<0.01). Conclusions Diverse types of particulate matters induce different pathological changes in the lungs, therefore the mechanism may also be different in the inflammatory responses. It means that the lung injuries caused by fine particles of mixed composition may have complex mechanisms.

Abstract:Objective To clone the coding sequence of Guangxi Bama mini-pig PGC-1α gene, and to analyze the expression of PGC-1α gene in various tissues of mini-pigs using RT-PCR and QRT-PCR techniques. Methods The PGC-1α gene coding sequence (CDS) was amplified by PCR from the cDNA of longissimus muscle of Guangxi Bama mini-pig. The PCR products were inserted into pEASY-T5 vector, transfected E. coli, identified and sequenced. The PGC-1α gene expression in different tissues of the Bama mini-pigs was detected by RT-PCR and QRT-PCR assays. Results The PGC-1α gene CDS of Guangxi Bama mini-pig was cloned. It was 2391 bp in length. It had 99.9% homology with the reference sequence, and had two synonymous mutations that were C-A1105 and G-A1524. The expression level of PGC-1α gene was higher in the heart and kidney, followed by liver, subcutaneous fat and longissimus muscle, but the expression was not detected in pancreas of Guangxi Bama mini-pig. Conclusions We have successfully cloned the PGC-1α gene of Guangxi Bama mini-pig, and detected this gene expression in six tissues. The results of this study will provide a basis for studying the effect of PGC-1α on type 2 diabetes mellitus (T2DM) in Bama mini-pigs.

Abstract:Objective To establish an optimal animal model of pulmonary metastasis of human lung adenocarcinoma, to serve further investigation of mechanism of lung adenocarcinoma metastasis. Methods Eleven nude mice aged 4-6 weeks were used in this study. Suspension of human lung adnocarcinoma A549 cells (0.1 mL, 10⁷ cells/mL) was injected into the tail vein in nude mice. From four weeks after inoculation, two nude mice were killed each time at 4, 5, 6 weeks after the tumor cell injection at random for examination. The remaining 3 mice were killed at the end of the experiment. At autopsy, the lung, brain, liver, kidney and other organs were removed, fixed in neutral buffered formalin and embedded in paraffin. Sections were cut and stained with hematoxylin-eosin, and examined by histopathology. The number of metastatic foci was counted. Results No mouse died after tumor cell inoculation. Serially euthanized mice revealed evidence of gradually increasing pulmonary metastases in the mice: No metastasis was found before 4 weeks after tumor cell inoculation, the first histological metastases appeared at 5 weeks, gross metastatic foci were observed at 6 weeks, widely spread metastatic foci were observed at 7 weeks, and the remain 3 mice developed cachesia at 11, 13, and 14 weeks after tumor cell inoculation. Mediastinal lymph node metastases were found in the nude mice by 11 weeks after tumor cell inoculation. Conclusions We have successfully established a nude mouse model of pulmonary metastasis by injecting human lung adenocarcinoma A549 cells into the tail vein.

Abstract:Objective To identify molecules that modulate T-cell functions and serve the studies on T-cell mediated autoimmune diseases. Methods Bone marrow-derived dentritic cells were collected from BALB/c mice to immunize Wistar rats, and to establish many hybridoma cell lines. Many hybridoma cell lines which could modulate T-cell functions were obtained. One of the cell lines, most actively inhibiting T-cell proliferation, was further studied. Results The anti-CD45 mAb recognized CD45 and significantly suppressed T-cell proliferation in proliferation assays. Conclusions Our results indicate that the anti-CD45 mAb can effectively suppress T-cell proliferation, and is promising to be used in the prevention and treatment of T-cell mediated autoimmune diseases in the future.

Abstract:Objective To explore the establishment of a rabbit model of atrial fibrillation by wireless telemetering and stimulation technology. Method An implantable telemetering stimulator which was independently designed and developed was hypodermically implanted in New Zealand rabbits. The implantable telemetering stimulator was made with the core development and design of MSP single-chip microcomputer of TI Corporation (Texas Instruments) and RF wireless transceiver chip CC2250 of TI Corporation. The design of the implantation system was optimized to cater to the exploratory experiment to establish atrial fibrillation model of New Zealand rabbits. The implanter was implanted into the abdominal subcutaneous tissue of the New Zealand rabbits, the collecting electrodes were placed in the oxter subcutaneous tissues of the left and the right upper extremities, and the two stimulating electrodes were sutured at the left auricle and the left atrium. The signals were collected and stimulated by the wireless transceiver. The I-lead ECG electrical signals were continuously monitored on the body surface by a Powerlab physiological recorder. High frequency (>20 Hz) suprathreshold stimulus (intensity 2 mA, pulse width 1 ms) was emitted by specialized stimulation software of a computer program by the interval (stimulating for 2 s and pausing for 2 s). In case of atrial fibrillation during intervals, the stimulation could be stopped by hand. In case of sinus rhythm, the stimulation could be continued. Results The implantable telemetering stimulator can work stably in vivo (including collecting stimulated electrocardio signal and emitting stimulations) for 30 days. Atrial fibrillation can be induced after stimulating in vivo of the New Zealand rabbits for 3 weeks, with a duration of >48 h. Conclusions Applying implantable telemetering stimulator can build a New Zealand istead of beagles model of atrial fibrillation which is more consistent with welfare optimization and substitution principle for laboratory animals.

Abstract:Objective To observe the effects of Astragalus polysaccharide (APS) on tumor growth, cytokine and immune function impairment induced by cisplatin (DDP) in mice bearing Lewis lung cancer. Methods A total of 90 mice were used in this study: 10 for blank control group, and 80 mice with transplanted Lewis lung cancer were randomly divided into 8 groups:model control group (physiological saline), positive control group treated with DDP (6 mg/kg), low dose APS (50 mg/kg), moderate dose APS (100 mg/kg) and high dose APS (200 mg/kg) groups and three combinations of APS+DDP groups (the same three APS levels with half dose of DDP, respectively). 0.3 mL of the drugs was intraperitoneally injected to the mice, respectively, on the second day after moldeling. DDP was injected once a week and other drugs were injected once per day for consecutive 20 days. On the 21st day, blood samples were collected and serum levels of cytokine IL-2, IL-6, IL-12 and TNF-α were determined by ELISA, and the tumor inhibition rate and immune organ indexes were assessed. Results The tumor inhibition rates of the positive control, low, moderate and high dose APS groups and three combinations of APS+DDP groups of mice bearing Lewis lung carcinoma were 49.30%, 17.21%, 39.68%, 17.21%, 51.02%, 57.21% and 65.11%, respectively. Compared with the model group, P<0.05 or P<0.01, and compared the three combination groups with the DDP group, P<0.05. Compared with the blank control group, the spleen index was significantly increased in the moderate and high dose APS groups and the three combinations of APS+DDP groups. There was a significant difference between the spleen indexes of the model control group, and the spleen indexes of high dose APS and the combination with high dose APS groups were significantly higher than that of the model control group (P<0.05). Compared with the DDP group, APS in various doses and combinations increased the thymus index and spleen index. Conclusions APS can improve the levels of cytokine IL -2, IL-6, IL-12 and TNF-α in mice bearing Lewis lung cancer, enhance the immune function impairment induced by DDP, has certain protective effect on the immune organs, and inhibit the growth of Lewis lung cancer in mice. When APS is used in combination with a half-dose of DDP, APS enhanced the inhibition of tumor growth. This mechanism may be related to the enhanced body immune function. Our results indicate that APS enhances the therapeutic effect of DDP and reduces its toxicity, therefore, may have potential application value in future treatment of solid tumors.

Abstract:Object This experiment was conducted to study the relationship between CFTR gene expression in the intestinal tissues and secretory diarrhea. Methods Twenty-four Kunming mice were selected, half male and half female, and were randomly divided into 3 groups (n=8 in each group): control group with intraperitoneal injection of 0.2 mL normal saline, and the experimental group of mice by intraperitoneal injection of lipopolysaccharide(LPS) (6 mg/kg·bw). The mental state and intestinal morphology of the mice at 1 h and 8 h after LPS injection were observed to assess whether the secretory diarrhea model was successfully established. The expression of CFTR gene segments of intestine tissue was detected by fluorescence quantitative PCR. Results LPS induced secretory diarrhea. CFTR gene was expressed in the mouse duodenum, jejunum, ileum and colon tissues with different expression abundance. It was highest in the colon, but the difference was not significant between intestinal segments. Compared with the control group, LPS up-regulated the transcription level of CFTR gene in the duodenum, jejunum and ileum, and down-regulated the transcription of CFTR gene in the colon. Conclusions The results of our study suggest that the changes of the transcriptional level of CFTR gene are closely related with the diarrhea induced by LPS and the effects in different intestinal segments on the diarrhea is different. The jejunum plays a crucial role and the colon plays a least role in the Cl^- secretion.

Abstract:Objective The aim of this study was to observe the effects of whole-body vertical vibration, treadmill exercise, genistein administration and estrogen injection on the uterus weight index and uterus histology as well as the expression of glycogen synthase kinase (GSK-3β) protein in the uterus of ovariectomized osteoporotic rats. Methods Seventy-two healthy 3-month old female SD rats were randomly divided into two groups by body weight: sham-operation group (Sham) and ovariectomized group (OVX). At 10 weeks after OVX operation, the OVX rats were randomly divided into the following five groups by body weight: OVX group, whole-body vertical vibration group (WBVV), treadmill exercise group (TX), genistein group (G) and 17β-estrogen group (E₂). Then they were treated with different methods according to the experiment design. At the end of experiment, the uterus weight was measured with an electronic balance. The uterus histology was observed with HE staining and the expressions of GSK-3β and P-GSK-3β proteins were detected by Western blot. Results Apart from E₂ treatment, all the other three treatments did not increase the uterus weight and the thickness of endometrium compared with that in the OVX rats. Apart from genistein treatment, all the other three treatments increased the ratio of protein expression of P-GSK-3β to GSK-3β compared with that in the OVX rats. Conclusions Both whole-body vertical vibration and treadmill exercise can stimulate the phosphorylation of GSK-3β in the uterus of OVX osteoporotic rats. However, genistein has no such stimulation effect.

Abstract:Objective To investigate the FH/Wjd rat model of alcoholic liver disease. Methods Thirty-six 16-18 week old SPF grade FH/Wjd rats (male:female=1:1) were used in this study. The rats were divided into two groups randomly by body weight: water intake group and alcohol intake group. The rats took water or alcohol freely. 16 weeks later, ALT, AST, TBIL, TG, CHO in the serum and TG, GSH in the liver homogenate were detected. The expression of PPARα protein in the liver tissue was detected by Western blot. The apoptosis rate of liver cells was assessed by flow cytometry. The pathological changes of liver tissue were examined using HE staining. Results Compared with the water intake group, the serum TBIL and TG were significantly increased in rats of both sexes of the alcohol intake group, moreover, ALT and CHO of the female rats in the alcohol intake group were significantly decreased. TG in the liver homogenate increased obviously, while GSH in the liver homogenate showed a decreasing tendency. Hepatocyte apoptosis in rats of both sexes in the alcohol intake group showed an increasing tendency. The PPARα protein expression was up-regulated obviously, and the main pathological change in the liver tissue was microvesicular fatty degeneration. Conclusion Spontaneous long-term alcohol intake can induce liver injuries in FH/Wjd rats.

Abstract:Objective To investigate the effect of heat stress on organ indices, intestinal morphology, gastric mucosal HSP70 mRNA expression and glucose metabolic hormones in mice. Methods A single-factor experiment was designed for the present research. Eighteen KM mice of the similar age and weight were randomly divided into control group and heat stress group. The weight of the heart, liver, spleen, lung and kidney, as well as the expression of HSP70 mRNA in the mouse gastric mucosa were measured. The plasma concentration of insulin and glucagon, the villus height and crypt depth of the duodenum and jejunum were detected. The histological changes of the liver, duodenum and jejunum were also examined. Results There was no effect of heat stress on the organ indices. It significantly increased the expression of HSP70 mRNA in the gastric mucosa, reduced the plasma insulin level and caused serious injury to the liver, duodenum and jejunum in the mice. Conclusions Heat stress does not significantly affect the organ indices in mice, but can significantly increase the expression of HSP70 mRNA in the gastric mucosa, cause apparent damages in the liver, duodenum and jejunum, reduce the villus height, crypt depth and villus height/crypt depth ratio of the duodenum and jejunum, and also decrease the blood insulin concentration in the mice.

Abstract:Objective To study whether the green fluorescent protein (GFP) gene can be successfully expressed in green fluorescent nude mice and the tissue distribution characteristics. Methods Small animal imaging system and RT-PCR assay were used to detect the GFP tissue distribution and fluorescence expression level. Results The GFP can be expressed in multiple tissues in green fluorescent nude mice. A higher expression was observed in the pancreas, heart, brain, and skin. Conclusion Exogenous GFP can be stably expressed and inherited in green fluorescent nude mice, with the highest expression in the pancreas.

Abstract:Objective To investigate the effect of testosterone on mitotic orientation in rat prostate epithelial cells and the relative differential gene expression. Methods Twenty SPF male SD rats were divided into 2 groups at random and then subjected to castration. One group of rats was administrated with testosterone 3.7 mg daily for 30 days and the control group was only injected with olive oil. Microscopic analysis was performed using immunohistochemistry. Differential gene expression analysis was conducted by gene microarray and RT-PCR techniques. Results In the testosterone-administrated group, there was a significant mitosis orientation parallel to the basement membrane. But in the control group, mitosis orientation was oriented perpendicular to the basement membrane. Using the gene microarray and RT-PCR techniques, the cell proliferation genes such as Ran, Tgm4 and Wnt2 in Wnt signal pathway were up-regulated in the testosterone group. Conversely, suppressor cell proliferation genes such as Dkk3 and Fas were down-regulated. Conclusions Mitotic orientation of prostate epithelia cells is changed after testosterone administration. Wnt signal pathway and AR singling pathway also have an influence on the mitosis orientation and cell proliferation.

Abstract:Objective To evaluate an improved modification of TTC staining method for measuring myocardial infarct size after ischemia-reperfusion in rats. Methods Twenty healthy SPF male 8-week-old SD rats were randomly divided into two groups: Group A with conventional TTC staining, and group B with the modified TTC staining method for measuring myocardial ischemia-reperfusion injury. The infarct size was caculated and the serum cTnI levels were determined. Results The infarcted myocardium was well detected in both groups A and B. There were no significant differences in the myocardial infarct sizes measured in the groups A and B (48.69±5.37 % vs. 47.41±3.28%, P>0.05). There were no significant differences in the serum cTnI levels assayed in the groups A and B (4.51±0.88 ng/mL vs. 4.70±0.71 ng/mL, P>0.05). But compared with the group A, the color contrast of stained myocardial slice and the distinguishing infarction area and non-infarction area were much clearer in the group B. Conclusions Our modified TTC staining technique using in vivo staining is an economic, convenient, fast and efficient method, being easy to control, time-saving and inexpensive, and enhances the staining effect in evaluating the size of myocardial ischemia/reperfusion injury more accurately.

Abstract:Objective To establish a mouse model of orthotopic Lewis lung carcinoma using Matrigel, to evaluate the tumor growth and metastasis, and to provide a more stable mouse model of orthotopic lung cancer, which is more similar to human lung cancer. Methods Logarithmic phase of cultured Lewis lung cancer cells were suspended in Matrigel, vaccinated into the left lung of inbred C57BL/6 mice. Five mice were killed on the 4th, 7th, 10th, 13th, and 16th days, respectively, and to observe the median survival, tumor formation rate, tumor growth, and metastasis. Pathological changes of the mouse lung, liver, kidney and spleen were examined. Results In 5 mice killed on the 7th postoperative day, small tumor nodules were observed on the lung in three mice and no tumor was visible by gross inspection in the other two mice, but small tumor nodules were observed under the microscope. For all the mice killed on the 10th postoperative day, tumors were visible to the naked eye on the lung of all the five mice. On the 13th day, orthotopic tumor was observed on the lung with bloody pleural effusion and pleural metastasis in all the five mice. On the 25th day, in addition to the pleural metastasis, one mouse had pericardial metastasis and renal metastasis. The survival periods of the 5 mice were 17 d, 20 d, 22 d, 22 d, and 25 d, respectively, with a median survival period of 21.2 d (17-25 d), and the tumor formation rate was 100%. Conclusions Mouse models of orthotopic Lewis lung carcinoma is successfully established using injection of tumor cells suspended in Matrigel. This model is more similar to the growth of human lung cancer, with good stability, high tumor formation rate and characteristics of distant metastasis, therefore, is worthy of further application.

Abstract:Objective To obtain a stably inherited Sprague-Dawley rat model of congenital umbilical hernia by inbreeding, and to observe the structure of umbilical hernia and treat it surgically. Methods Congenital umbilical hernia rats were fostered by full-sib mating. The birth number and umbilical hernia quantity were recorded, and the umbilical hernia rate of rats was analyzed. Six female and 6 male rats with congenital umbilical hernia of 6-month aged F₂ generation were selected randomly, among which 2 female and 2 male rats were examined anatomically, and the rest rats underwent surgical suture. Results The umbilical hernia rate was increased along with the increasing inbreeding coefficient, and the rats of F₁₂and F₁₃ generations were all with congenital umbilical hernia. The umbilical hernia rate in female rats was significantly higher than that in male rats based on the total number of rats from F₁ to F₁₃ generation (χ²=11.1, P=0.001). Female and male rats had the same structure of umbilical hernia, and all rats recovered 3-4 weeks after surgery without recurrence. Conclusion After 13 consecutive generations of full-sib mating, a rat model of congenital umbilical hernia with stable genetic properties is successfully established.

Abstract:Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in humans. Due to the lack of suitable experimental animal models for HCV infection, the development of more effective treatment of HCV infection and vaccines has been delayed. Chimpanzee is the best experimental animal model for the research of hepatitis C virus (HCV) infection. However, because of its limited in resource, expensive in breeding, and difference in clinical symptoms, thus developing new experimental animal models for HCV-related basic and applied research is imminent. In recent years, as a surrogate animal model, the development of rodent model and other models has been achieved a lot of progress. Using such as genetically modified experimental techniques, those surrogate animals were infected with HCV in vivo and were successfully applied to research in several areas. In this review, we will focus on the achieved progress in naturally infected animal model and transgenic surrogate experimental models, and their advantage and limitation in usage in study on the pathogenetic mechanism of infection, drug evaluation and development of vaccines, and will also discuss the future direction of development of experimental animal models for research of infection with HCV.

Abstract:Liver diseases post great threats to human public health globally. Lacking of appropriate small animal models largely impeded the translational studies on human liver diseases, especially on viral hepatitis and related cirrhosis, hepatocellular carcinoma, etc. By human hepatocyte transplantation, the liver-humanized mice have significantly contributed to the researches of human liver diseases. This review summarizes the currently widely used and representative humanized mouse models, including uPA, FAH, TK-NOG, AFC8 mice and their applications in studies of human liver diseases.

Abstract: