ABSTRACT
Objective:To compare the effect and mechanisms of modified Erchentang and Xuefu Zhuyutang on high-fat diet-induced apolipoprotein-E knockout (ApoE-/-) mice nonalcoholic fatty liver disease (NAFLD). Method:Ten C57/BL6J mice were taken as normal control group and fed with normal feed. Totally 30 ApoE-/- mice were fed with high-fat diet to establish a disease model for 4 weeks. After 4 weeks, the 30 ApoE-/- mice were divided into model group, Xuefu Zhuyutang group (hereinafter referred to as Huoxue group) and modified Erchentang group (hereinafter referred to as Huatan group) by random number table method, with 10 in each group. The normal group and the model group were intragastrically administered with normal saline. The drug-administered group was intragastrically administered at a dosage that was ten times of the adult dose, once a day, for 8 weeks. Serum and liver were collected after the end of the 12-week experiment. The serum lipid and liver function levels of each group were measured, and the liver pathological morphology was observed. Protein and mRNA expressions of liver inflammatory mediators interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic factor-1 (MCP-1) were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result:The results of serum lipids and liver function showed that compared with the normal group, serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the model group were significantly increased, while serum high-density lipoprotein (HDL) was significantly reduced (P<0.01). Compared with the model group, serum TG ，LDL and ALT were significantly decreased, HDL was significantly increased in the Huoxue group (P<0.05). The serum levels of TC, TG， LDL, AST and ALT in the Huatan group were significantly decreased，HDL was significantly increased (P<0.05，P<0.01), and TG was decreased. The mice serum HDL in the Huatan group was higher than that in the Huoxue group. The serum ALT in the Huoxue group was lower than that in the Huatan group. The pathological observation showed that compared with the normal group, hepatocytes in the model group had severe steatosis with many lipid droplet vacuoles, suggesting that the mouse NAFLD model was successful. Compared with the model group, each administration group alleviated hepatocyte steatosis, with no significant difference between the two administration groups. Western blot and Real-time PCR results showed that compared with the normal group, protein and mRNA expression levels of TNF-α, IL-1β, MCP-1, and MMP-9 in the model group were significantly increased (P<0.05，P<0.01). Compared with the model group, the Huoxue group significantly down-regulated the expressions of IL-1β, MCP-1 protein and MCP-1 mRNA(P<0.05，P<0.01). The Huatan group significantly reduced the expressions of IL-1β, TNF-α, MMP-9, MCP-1 protein, TNF-α and MMP-9 mRNA(P<0.05，P<0.01). Conclusion:Modified Erchentang and Xuefu Zhuyutang can alleviate the therapeutic effect of NAFLD mice to a certain extent, modified Erchentang has a better therapeutic effect.