基于Ras/ERK信号通路的四君子汤对大鼠肝癌抑制作用及机制分析OA

Objective To observe the therapeutic effect of the classical traditional Chinese medicine formula Sijunzi Decoction on rats with hepatocellular carcinoma(HCC)and to analyze its potential mechanism from the perspective of the rat sarcoma viral oncogene homolog(Ras)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods Fifty SD rats were randomly divided into 5 groups:normal group,model group,low-dose Sijunzi Decoction group,high-dose Sijunzi Decoction group,and high-dose Sijunzi Decoction+ML-099(Ras/ERK pathway activator)group,with 10 rats in each group.Except for the normal group,rats in the other groups received intraperitoneal injections of diethylnitrosamine(DEN)to establish the HCC model.After successful modeling,the groups received the respective interventions.Following the intervention,liver index was calculated in each group.Serum levels of liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)]and inflammatory factors[interleukin(IL)-1α,chemokine ligand 2(CCL-2),and IL-6]were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe histopathological changes in liver tissue.The expression levels of apoptosis-related proteins[cleaved cysteine aspartate protease 3(cleaved-Caspase 3),B-cell lymphoma/leukemia-2 gene(Bcl-2)]and Ras/ERK signaling pathway-related proteins[Ras and phosphorylated(p)-ERK/ERK]in liver tissue were detected by Western Blot.Results Compared with the normal group,the model group exhibited significantly increased liver index,serum levels of ALT,AST,ALP,IL-1α,CCL-2,and IL-6,as well as elevated expression levels of cleaved-Caspase 3,Bcl-2,Ras,and p-ERK/ERK(P＜0.05),while the expression level of Bax was significantly decreased(P＜0.05).Compared with the model group,both the low-dose and high-dose Sijunzi Decoction groups showed significantly reduced,liver index,serum levels of ALT,AST,ALP,IL-1α,CCL-2,and IL-6,and decreased expression levels of cleaved-Caspase 3,Bcl-2,Ras,and p-ERK/ERK(P＜0.05),along with a significantly increased expression level of Bax(P＜0.05),in a dose-dependent manner.Compared with the high-dose Sijunzi Decoction group,the high-dose Sijunzi Decoction+ML-099 group demonstrated significantly increased,liver index,serum levels of ALT,AST,ALP,IL-1α,CCL-2,and IL-6,and elevated expression levels of cleaved-Caspase 3,Bcl-2,Ras,and p-ERK/ERK(P＜0.05),while the expression level of Bax was significantly decreased(P＜0.05).Conclusion Sijunzi Decoction can improve liver function and alleviate liver injury in rats with HCC,and its mechanism of action may be associated with inhibiting the Ras/ERK signaling pathway,ameliorating inflammatory responses,and promoting cancer cell apoptosis.