Therapeutical effect of Toudingyikezhu extract on rats with nonalcoholic fatty liver and its mechanism / 吉林大学学报(医学版)

ABSTRACT

Objective:To observe the effect of Toudingyikezhu extract on the morphology of liver tissue and endoplasmic reticulum stress(ERS) of the rats with nonalcoholic fatty liver disease(NAFLD),and to clarify the possible mechanism of Toudingyikezhu of intervention of NAFLD.Methods:The NAFLD rat models were established by intraperitoneal injection of carbon tetrachloride solution combined with high-fat diet.A total 60 SD rats were randomly divided into control group,model group,low,middle and high doses of Toudingyikezhu extract groups,phosphatidylcholine group(n=10).The doses of Toudingyikezhu extracts were 0.50,1.00 and 2.00 g·mL-1,and the dose of phosphatidylcholine was 0.20 g·kg-1,4 weeks after administration,the body weights and liver wet weights were detected,and the liver indexes were calculated.The texture,elasticity,color and morphology of liver tissue of the rats were observed by HE staning.The fatty degeneration,inflammation and necrosis scores of liver tissue of the rats were calculated.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1 (IL-1) and interleukin-6(IL-6) of the rats were detected by ELISA method.Immunohistochemical SP method was used to determine the expression levels of GRP78 protein,and PCR method was used to determine the expression levels of GRP78 mRNA.Results:Compared with control group,the morphology of liver tissue of the rats in model group were abnormal under light microscope;the liver index,fatty degeneration,inflammation and necrosis scores of liver tissue of the rats in model group were increased(P<0.05),and the expression levels of GRP78 protein and mRNA were decreased(P<0.01).Compared with model group,the liver tissue pathology of the rats had different degrees of improvement;the fatty degeneration,inflammation and necrosis scores of liver tissue and the serum TNF-α,IL-1,IL-6 levels of the rats in different doses of Toudingyikezhu extract groups were decreased(P<0.05 or P<0.01);the expression levels of GRP78 protein and mRNA were decreased (P <0.05 or P<0.01).Conclusion:Toudingyikezhu extract may inhibit or block the ERS,reduce the synthesis of lipids and accelerate its decomposition in order to resist the injury of liver cells of the NAFLD rats by down-regulating the GRP78 expression.