健脾疏肝方对非酒精性脂肪性肝病模型大鼠PI3K/AKT/HIF-1α信号通路表达的影响OA

Objective To investigate the effects of Jianpi Shugan Prescription on the expressions of PI3K,AKT,mTOR,HIF-1α and VEGFA in liver tissue of non-alcoholic fatty liver disease(NAFLD)model rats;To explore the mechanism by which Jianpi Shugan Prescription regulates lipid metabolism disorder in NAFLD rats.Methods A total of 60 SD rats were randomly divided into control group(12 rats)and high-fat diet group(48 rats),which were respectively fed with a normal diet and a high-fat diet for 8 weeks to establish the NAFLD model.After the model was successfully established,the rats in the high-fat diet group were randomly assigned into model group,simvastatin group and Jianpi Shugan Prescription high-and low-dosage groups.Each group was administered the corresponding drugs via gavage for 6 weeks.The contents of serum lipid-related indexes and liver function-related indexes(TC,TG,HDL-C,LDL-C,ALT and AST)were determined,HE staining was employed to observe the morphology of liver tissue,and oil red O staining was utilized to observe the liver lipid accumulation,the contents of liver lipid metabolism enzymes of SREBP-1c,FASN,HMGCR and LDLR were measured by ELISA,the mRNA expressions of PI3K,AKT,mTOR,HIF-1α and VEGFA in liver tissue were detected by RT-PCR.Results Compared with the control group,the liver wet weight and liver index of the model group significantly increased(P<0.01),the contents of serum TC,TG,LDL-C,ALT,AST and SREBP-1c,FASN,HMGCR in liver tissue significantly increased(P<0.01),and the contents of serum HDL-C and LDLR in liver tissue significantly decreased(P<0.01);the liver presented obvious steatosis and increased lipid accumulation;the mRNA expression of PI3K,AKT,mTOR,HIF-1α and VEGFA in liver tissue significantly increased(P<0.01).Compared with the model group,the liver wet weight and liver index of rats in Jianpi Shugan Prescription high-dosage group and simvastatin group significantly decreased(P<0.05,P<0.01),and the contents of serum TC,TG,LDL-C,ALT,AST and SREBP-1c,FASN,HMGCR in liver tissue significantly decreased,while the contents of serum HDL-C and LDLR in liver tissue significantly increased(P<0.05,P<0.01);the degree of liver steatosis and lipid accumulation was alleviated;the mRNA expressions of PI3K,AKT,mTOR,HIF-1α and VEGFA in liver tissue were significantly increased(P<0.01).Conclusion Jianpi Shugan Prescription may regulate the levels of SREBP-1c,FASN,HMGCR,LDLR,improve lipid metabolism disorder,reduce liver lipid accumulation,and play a role in the treatment of NAFLD by inhibiting the expressions of PI3K/AKT/HIF-1α signaling pathway related molecules in NAFLD model rats.