Mechanism study of Qushi Huayu Decoction inhibiting Wnt3a/β-catenin/VEGF signaling pathway to protect gut vascular barrier in treatment of experimental NAFLD
Objective:To reveal the mechanism of treatment of non-alcoholic fatty liver disease(NAFLD)by Qushi Huayu Decoction by observing the effect of Qushi Huayu Decoction on ileocecal gut vascular barrier function in NAFLD mice.Methods:①Using high-fat and high-carbohydrate(HFHC)diet model,C57BL/6J mice were randomly divided into normal group,HFHC model group,and Qushi Huayu Decoction low-dose and high-dose groups.The drug was administered at the end of 12 weeks until the end of 18 weekends;②the mice were examined for TG of the liver tissues,serum biochemical indices;HE staining to observe the pathology of liver tissue and ileum;Lipid in liver tissue was observed by oil red O staining;Immunofluorescence to observe the expression of ileal PV-1;Western Blot to detect the expression of hepatic LBP and ileal Wnt3a,p-β-catenin,VEGF.Results:Compared with the normal group,liver TG,serum ALT,AST activity,liver NAS score,serum TG,TC,LDL-C,fasting blood glucose,fasting insulin and HOMA-IR were significantly elevated in the model group of mice(P＜0.01),after the intervention of Qushi Huayu Decoction,it was significantly reduced(P＜0.05,P＜0.01).In the model group,HE staining of liver tissue showed that the outline of liver cells was swollen,irregular shape,steatosis,ballooning and inflammatory cell infiltration were common.HE staining of the ileum showed that the structure of the ileum was damaged and a small number of cells at the top of the villi were shed.Oil red O staining of liver tissue showed that the outline of liver cells became large and round,and a large number of lipid droplets could be seen in the cytoplasm.Immunofluorescence results of PV1 in ileum showed that PV1 expression was significantly increased(P＜0.01).Western Blot results showed that the expressions of LBP in liver,Wnt3a in ileum,p-β-catenin/β-catenin and VEGF were significantly increased(P＜0.05,P＜0.01).After the intervention of Qushi Huayu Decoction,the liver tissue and ileum pathology were improved,the lipid droplets in hepatocytes were significantly smaller,the expression of PV1 in ileum was significantly decreased(P＜0.05),and the expressions of liver LBP,ileum Wnt3a,p-β-catenin/β-catenin and VEGF were significantly decreased(P＜0.05,P＜0.01).Conclusion:Qushi Huayu Decoction can protect the function of gut vascular barrier and improve NAFLD by inhibiting the Wnt3a/β-catenin/VEGF signaling pathway and down-regulating the expression of PV1 in the ileum.
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