【Animal Modeling】-How to compare the two compound mouse models of hepatitis B hepatitis B fibrosis?

  Purpose: C57BL/6N-Tg (1.28HBV)/Vst hepatitis B virus transgenic mice and rAAV8-1.3HBV adeno-associated virus transfected mice combined with intraperitoneal injection of carbon tetrachloride, hepatitis B liver fibrosis using a mouse model, guide you to compare The virological and biochemical pathological characteristics of the two mouse models?

  Method: Experiment in wild type control group (WT), rAAV8-1.3HBV transfection group (rAAV), CCl4 group (CCl4), rAAV8-1.3HBV. Divided into composite CCl4 models. Group (rAAV) + CCl4), C57BL/6N-Tg (1.28HBV)/Vst hepatitis B virus transgenic group (Tg), transgenic compound CCl4 group (Tg+CCl4), the model was built for 12 weeks? Serum HBsAg, HBeAg levels , Fluorescence quantitative PCR detection of serum HBV-DNA load, liver tissue paraffin section immunohistochemical staining, observation of liver HBsAg and HBcAg expression, serum ALT? kit AST? AKP biochemical detection, hydroxyproline detection in liver tissue by hydrochloric acid hydrolysis (Hyp) content? HE staining and Sirius observation of inflammation, collagen red staining and other pathological changes?

  Results: Except for the WT group and the CCl4 group, the ELISA test of serum HBsAg and HBeAg were all positive, and the HBV-DNA fluorescence quantitative PCR test was higher than 1.0×104 IU/mL?Tg+CCl4 group. The HBsAg?HBeAg content was higher than that of Tg+CCl4 The HBV-DNA level of rAAV + CCl4 group is higher than Tg? Is HBcAg positive in Tg + CCl4 group? HBsAg expression in AAV group is lower than that in Tg group; HBcAg expression in rAAV group is significantly higher than that in Tg group? The results of HBsAg were different, and the positive expression of HBcAg in the rAAV+CCl4 group was significantly increased. The biochemical results showed that CCl4 group, Tg+CCl4 group, rAAV+CCl4 group, serum ALT, AST and liver tissue virus Hyp content increased significantly; among them, the Hyp content of Tg+CCl4 group was higher than that of rAAV+CCl4 group? Is there a significant difference between the AKP results and the WT group? The pathological results showed that inflammation and collagen deposition in the AAV and Tg groups were not obvious in the WT group; inflammation and collagen deposition in the CCl4 group? Tg+CCl4 group? RAAV+CCl4 group. RAAV+ in the Tg+CCl4 group. Is it higher than the CCl4 group?

  Conclusion: Do the two composite models meet the requirements of the hepatitis B liver fibrosis model, and the differences are mainly concentrated in viral indicators and pathological changes? Is the rAAV+CCl4 group beneficial to the loading of HBV-DNA? Tg + CCl4 group shows more obvious fibrosis progression?