抗纤抑癌方对肝癌前病变大鼠整合素α5β1/FAK信号通路的影响

Effects of Kangxian Yi'ai Formula on integrin α5β1/FAK signaling pathway in rats with hepatic precancerous lesions

目的:基于整合素α5β1/FAK信号通路探讨抗纤抑癌方干预肝癌前病变的作用机制。方法:雄性Wistar大鼠85只,随机分为正常组、模型组、抗纤抑癌低、中、高剂量组及鳖甲软肝组。采用二乙基亚硝胺腹腔注射制备肝癌前病变模型,用抗纤抑癌方进行干预,以复方鳖甲软肝片作为对照;采用HE、Masson染色观察大鼠肝脏组织病理情况,实时荧光定量PCR及Western blot法检测肝组织中ITG-α5、ITG-β1、FN及FAK mRNA及蛋白的表达水平。结果:抗纤抑癌方可明显改善大鼠肝脏组织纤维化程度,降低肝细胞的变性、坏死;与模型组相比,抗纤抑癌中、高剂量组能显著降低ITG-α5、ITG-β1、FN、FAK mRNA的表达及ITG-α5、ITG-β1蛋白的表达(P<0.01,P<0.05);与鳖甲软肝组相比,抗纤抑癌中、高剂量组能显著降低ITG-α5、ITG-β1、FN mRNA的表达及ITG-β1蛋白的表达(P<0.05)。结论:抗纤抑癌方可通过调控整合素α5β1/FAK信号抑制肝癌前病变。

Objective: To explore the mechanism of Kangxian Yi’ai Formula in the intervention of precancerous lesions of the liver based on integrin α5β1/FAK signaling pathway. Methods: Eighty-five male Wistar rats were randomly divided into the normal group, model group, Kangxian Yi’ai Formula low dose, medium dose and high dose group, and Biejia Ruangan group. The animal model of hepatic precancerous lesions was induced by diethylnitrosamine. Kangxian Yi’ai Formula was used to intervene. Biejia Ruangan Tablets were taken as a control drug. The pathological changes of liver tissues were observed by HE and Masson staining. The expression of ITG-α5, ITG-β1, FN, FAK mRNA and protein in liver tissues was detected by real-time fluorescence quantitative PCR and Western blot method. Results: Kangxian Yi’ai Formula could significantly ameliorate hepatic fibrosis and reduce hepatocyte degeneration and necrosis. Compared with the model group, the expression of ITG-α5, ITG-β1, FN, FAK mRNA and the expression of ITG-α5, ITG-β1 protein in the Kangxian Yi’ai middle dose and high dose groups were significantly decreased(P<0.01, P<0.05). The expression of ITG-α5, ITG-β1, FN mRNA, and ITG-β1 protein in the Kangxian Yi’ai middle dose and high dose groups were significantly lower than that in the Biejia Ruangan Group(P<0.05). Conclusion: Kangxian Yi’ai Formula could delay the occurrence of hepatic precancerous lesions by regulating the integrin α5β1/FAK signaling pathway.