丁香苷调节Hedgehog-YAP1信号通路对肝硬化大鼠纤维化的影响  

Impact of Syringin on the Fibrosis of Cirrhotic Rats by Regulating Hedgehog-YAP1 Signal Pathway

作　　者：吴德建 杨秋 谢桂丹 彭鑫 WU Jiande;YANG Qiu;XIE Guidan;PENG Xin(Digestive System Department,Danzhou People's Hospital,Danzhou 571799,China;Laboratory Department,Western Central Hospital of Hainan,Danzhou 571799,China)

机构地区：[1]詹州市人民医院,消化内科,詹州571799 [2]海南西部中心医院,检验科,詹州571799

出　　处：《中国细胞生物学学报》2025年第4期858-866,共9页Chinese Journal of Cell Biology

基　　金：海南省卫生健康行业科研项目(批准号:22A200156)资助的课题。

摘　　要：为了探讨丁香苷调节Hedgehog-Yes相关蛋白(YAP)信号通路对肝硬化大鼠纤维化的影响,取SD大鼠腹腔注射四氯化碳(CCl_4)构建肝硬化模型,随机分为模型组、丁香苷低剂量组、丁香苷高剂量组、Purmorphamine(Hedgehog激活剂)组、丁香苷高剂量+Purmorphamine组,另选大鼠设为对照组,以丁香苷和Purmorphamine分组处理后,检测肝指数及肝功能指标谷丙转氨酶(ALT)、天冬氨酸氨基转移酶(AST)水平;采用Masson染色检测肝硬化大鼠肝组织纤维化情况;采用试剂盒测量各组肝硬化大鼠肝组织羟脯氨酸(HYP)含量,肝组织与血清TNF-α、IL-6、MDA,总抗氧化能力(TAC)水平;采用免疫印迹检测各组肝硬化大鼠肝组织胶原蛋白collagen I、collagen I表达及Hedgehog-YAP1信号相关蛋白表达情况。结果显示,与对照组相比,模型组大鼠肝指数, ALT水平,AST水平,血清TNF-α水平、IL-6水平、MDA水平,肝组织TNF-α水平、IL-6水平、MDA水平、胶原纤维占比、HYP含量、collagen I蛋白表达水平、collagen III蛋白表达水平、Hedgehog蛋白表达水平及p-YAP1/YAP1升高(P<0.05),肝组织与血清TAC水平降低(P<0.05)。与模型组相比,丁香苷低和高剂量组大鼠肝指数, ALT水平, AST水平,血清TNF-α水平、IL-6水平、MDA水平,肝组织TNF-α水平、IL-6水平、MDA水平、胶原纤维占比、HYP含量、collagen I蛋白表达水平、collagen III蛋白表达水平、Hedgehog蛋白表达水平及p-YAP1/YAP1降低(P<0.05),肝组织与血清TAC水平均升高(P<0.05),且高剂量丁香苷作用更强。Purmorphamine组大鼠各指标变化趋势与丁香苷低、高剂量组相反,且Purmorphamine可逆转丁香苷对模型组大鼠各指标的作用。这表明丁香苷可通过阻止Hedgehog-YAP1信号激活而抑制炎症及氧化应激,从而减轻肝硬化大鼠肝纤维化,改善其肝功能。In order to investigate the impact of syringin on the fibrosis of cirrhotic rats by regulating Hedgehog-YAP1(Yes-associated protein 1)signal pathway,SD rats were randomly divided into model group,low-dose syringin group,high-dose syringin group,Purmorphamine(Hedgehog activator)group,high-dose syringin+Purmorphamine group,another rats were selected as the control group,the liver index and liver function indexes[ALT(alanine aminotransferase)and AST(aspartate aminotransferase)]were measured after treatment with syringin and Purmorphamine;the hepatic fibrosis was detected by Masson staining in cirrhotic rats;the content of HYP(hydroxyproline)in liver tissue,and the levels of TNF-α,IL-6,MDA and TAC(total antioxidant capacity)in liver tissue and serum of cirrhotic rats in each group were measured with the kit;Western blot was used to detect the expression of collagen I,collagen II and Hedgehog-YAP1 signal related protein in liver tissues of cirrhotic rats in each group.The results show that,compared with the control group,the liver index,the levels of ALT and AST,the levels of TNF-α,IL-6,and MDA in serum,the content of HYP in liver tissue,the proportion of collagen fibers in liver tissue,the levels of TNF-α,IL-6,and MDA in liver tissue,the expression of collagen I,collagen III,Hedgehog proteins in liver tissue and p-YAP1/YAP1 in liver tissue in model group increased(P<0.05),while the level of TAC in serum and in liver tissue decreased(P<0.05).Compared with the model group,the levels of TNF-α,IL-6,and MDA in serum,the content of HYP in liver tissue,the proportion of collagen fibers in liver tissue,the levels of TNF-α,IL-6,and MDA in liver tissue,the expression of collagen I,collagen III,Hedgehog proteins in liver tissue and p-YAP1/YAP1 in liver tissue in the low-dose and high-dose syringin groups decreased(P<0.05),the level of TAC increased(P<0.05),and the effect of high dose syringin is stronger.The change trend of each index of rats in the Purmorphamine group is contrary to that in the low and high dose groups of

关 键 词：丁香苷 Hedgehog-YAP1 肝硬化 纤维化 

分 类 号：R285.5[医药卫生—中药学]