Objective: To study the protective effect of ruanganyin on the liver of HBV transgenic mice. Methods: 50 half HBV transgenic mice, male and female, were randomly divided into treatment group (high, medium and low dose...Objective: To study the protective effect of ruanganyin on the liver of HBV transgenic mice. Methods: 50 half HBV transgenic mice, male and female, were randomly divided into treatment group (high, medium and low dose Ruanganyin), model group, positive control group (entecavir dispersible tablet) and 10 non HBV transgenic mice as blank control. The mice were killed after 4 weeks of drug intervention.The serum levels of ALT, AST, TBIL, LN, HA, IV-C and PCIII were observed. Results: (1) compared with the blank control group, the ALT,AST and TBIL levels in the model group were significantly higher than those in the blank control group (P < 0.01);compared with the model group, the ALT, AST and TBIL levels in the high-dose group of ruanganyin after treatment were significantly lower than those in the model group (P<0.01/P<0.05);the ALT, AST and TBIL levels in the positive control group were lower than those in the model group (P<0.01/P<0.05) There was no significant difference in ALT, AST and TBIL levels between the two groups (P>0.05). (2) Compared with the blank control group, the level of LN, HA, IV-C and PCIII in the model group was significantly higher than that in the blank control group (P<0.01);compared with the model group, the level of LN, HA and IV-C in the high-dose group and the positive control group after treatment was significantly lower than that in the model group (P<0.01);the level of PCIII in the high-dose group and the positive control group after treatment was significantly lower than that in the model group (P<0.01);There was no significant difference in LN, HA, IV-C and PCIII levels between the two groups (P> 0.05). Conclusion: Chinese medicine Ruanganyin has the effects of protecting liver, reducing enzyme and anti fibrosis, but its mechanism of anti fibrosis needs further study.展开更多
BACKGROUND: Worldwide, about 25% of individuals with chronic hepatitis B have fatty liver disease. Lipogenic diets that are completely devoid of methionine and choline induce nonalcoholic fatty liver disease. However,...BACKGROUND: Worldwide, about 25% of individuals with chronic hepatitis B have fatty liver disease. Lipogenic diets that are completely devoid of methionine and choline induce nonalcoholic fatty liver disease. However, no animal model of nonalcoholic steatohepatitis associated with HBV infection is available, and the influence of viral infection on nutritional hepatic steatosis is unclear. METHODS: We used HBV surface antigen transgenic mice (HBs-Tg mice), which mimic healthy human carriers with hepatitis B surface antigen. The mice were fed with a high-fat methionine-choline-deficient diet (MCD) to build a reliable rodent nutritional model of nonalcoholic steatohepatitis associated with HBV infection, and the changes in body weight and serum triglycerides were measured. Hepatocyte ballooning changes were determined by hematoxylin and eosin staining. The extent of hepatic fat accumulation was evaluated by oil red O staining. Immunohistochemical assays were performed to detect proliferating cell nuclear antigen as an index of cell proliferation. RESULTS: MCD feeding provoked systemic weight loss and liver injury. MCD feeding caused more macrovesicular fat droplets and fat accumulation in the livers of HBs-Tg mice than in wild-type C57BL/6 mice. In addition, within 30 days of MCD exposure, more PCNA-positive nuclei were found in the livers of HBs-Tg mice. CONCLUSIONS: HBs-Tg mice fed with a lipogenic MCD form more macrovesicular fat droplets earlier, coincident with more hepatocyte proliferation, resulting in the appearance of increased susceptibility to experimental steatohepatitis in these mice.展开更多
目的:观察在肝损伤早期,拉米夫定和水飞蓟素对酒精刺激的乙型肝炎病毒(hepatitis B virus,HBV)转基因小鼠肝组织保护作用,并通过检测肝纤维化相关因子探讨其机制。方法:将40只1.3拷贝HBV转基因BALB/C小鼠随机分为4组。对照组以生理盐水...目的:观察在肝损伤早期,拉米夫定和水飞蓟素对酒精刺激的乙型肝炎病毒(hepatitis B virus,HBV)转基因小鼠肝组织保护作用,并通过检测肝纤维化相关因子探讨其机制。方法:将40只1.3拷贝HBV转基因BALB/C小鼠随机分为4组。对照组以生理盐水灌胃;模型组以体积分数为50%的白酒5 m L/kg灌胃,1次/d;拉米夫定组在模型组处理基础上以拉米夫定溶液(100 mg/kg)灌胃,1次/d;水飞蓟素组在模型组处理基础上以水飞蓟素溶液(200 mg/kg)灌胃,1次/d。10周后荧光定量PCR检测各组小鼠血清HBV-DNA载量,全自动生化仪检测血清ALT和AST水平。HE染色,Masson染色镜检观察肝组织病理变化,荧光实时定量PCR检测肝组织TGF-β1,Smad3,Smad7,结缔组织生长因子(connective tissue growth factor,CTGF)mRNA表达水平,免疫组织化学检测肝组织TGF-β1,CTGF,α-平滑肌肌动蛋白(α-SMA)表达水平。结果:与对照组相比,模型组肝组织病理损伤加重,血清HBV病毒载量,ALT和AST水平明显增高,肝组织内TGF-β1,Smad3,Smad7,CTGF mRNA及TGF-β1,CTGF,α-SMA蛋白表达增加(P<0.05)。与模型组相比,拉米夫定组和水飞蓟素组肝组织病理损伤均减轻,肝组织内TGF-β1,Smad3,CTGF mRNA及TGF-β1,CTGF,α-SMA蛋白表达减少(P<0.05),Smad7 mRNA的表达进一步增加(P<0.05),水飞蓟素组血清ALT和AST水平降低(P<0.05)。结论:拉米夫定和水飞蓟素可通过调节TGF-β1/Smads信号通路,减少CTGF表达,抑制肝星状细胞活化等机制阻断酒精刺激的HBV转基因小鼠肝组织纤维化的发生和进展。展开更多
文摘Objective: To study the protective effect of ruanganyin on the liver of HBV transgenic mice. Methods: 50 half HBV transgenic mice, male and female, were randomly divided into treatment group (high, medium and low dose Ruanganyin), model group, positive control group (entecavir dispersible tablet) and 10 non HBV transgenic mice as blank control. The mice were killed after 4 weeks of drug intervention.The serum levels of ALT, AST, TBIL, LN, HA, IV-C and PCIII were observed. Results: (1) compared with the blank control group, the ALT,AST and TBIL levels in the model group were significantly higher than those in the blank control group (P < 0.01);compared with the model group, the ALT, AST and TBIL levels in the high-dose group of ruanganyin after treatment were significantly lower than those in the model group (P<0.01/P<0.05);the ALT, AST and TBIL levels in the positive control group were lower than those in the model group (P<0.01/P<0.05) There was no significant difference in ALT, AST and TBIL levels between the two groups (P>0.05). (2) Compared with the blank control group, the level of LN, HA, IV-C and PCIII in the model group was significantly higher than that in the blank control group (P<0.01);compared with the model group, the level of LN, HA and IV-C in the high-dose group and the positive control group after treatment was significantly lower than that in the model group (P<0.01);the level of PCIII in the high-dose group and the positive control group after treatment was significantly lower than that in the model group (P<0.01);There was no significant difference in LN, HA, IV-C and PCIII levels between the two groups (P> 0.05). Conclusion: Chinese medicine Ruanganyin has the effects of protecting liver, reducing enzyme and anti fibrosis, but its mechanism of anti fibrosis needs further study.
基金supported by grants from the National Natural Science Foundation of China (30730084 and 30721002)the National Key Basic Research Program of China (973 Program) (2009CB522403,2007CB512405,and 2007CB512807)
文摘BACKGROUND: Worldwide, about 25% of individuals with chronic hepatitis B have fatty liver disease. Lipogenic diets that are completely devoid of methionine and choline induce nonalcoholic fatty liver disease. However, no animal model of nonalcoholic steatohepatitis associated with HBV infection is available, and the influence of viral infection on nutritional hepatic steatosis is unclear. METHODS: We used HBV surface antigen transgenic mice (HBs-Tg mice), which mimic healthy human carriers with hepatitis B surface antigen. The mice were fed with a high-fat methionine-choline-deficient diet (MCD) to build a reliable rodent nutritional model of nonalcoholic steatohepatitis associated with HBV infection, and the changes in body weight and serum triglycerides were measured. Hepatocyte ballooning changes were determined by hematoxylin and eosin staining. The extent of hepatic fat accumulation was evaluated by oil red O staining. Immunohistochemical assays were performed to detect proliferating cell nuclear antigen as an index of cell proliferation. RESULTS: MCD feeding provoked systemic weight loss and liver injury. MCD feeding caused more macrovesicular fat droplets and fat accumulation in the livers of HBs-Tg mice than in wild-type C57BL/6 mice. In addition, within 30 days of MCD exposure, more PCNA-positive nuclei were found in the livers of HBs-Tg mice. CONCLUSIONS: HBs-Tg mice fed with a lipogenic MCD form more macrovesicular fat droplets earlier, coincident with more hepatocyte proliferation, resulting in the appearance of increased susceptibility to experimental steatohepatitis in these mice.
