基于Hippo-YAP/TAZ途径探讨丹参酮ⅡA对肝硬化大鼠肝纤维化的改善作用实验研究OA
Improvement effect of Danshenide ⅡA on liver fibrosis in liver cirrhosis rats based on Hippo-YAP/TAZ pathway
目的:探讨丹参酮Ⅱ A(Tan Ⅱ A)对肝硬化大鼠肝脏纤维化的改善作用,并基于Hippo-Yes相关蛋白(YAP)/含PDZ结合基序的转录共激活因子(TAZ)途径分析其潜在作用机制.方法:腹腔注射40％四氯化碳花生油混悬液诱导肝硬化大鼠模型.将造模成功的大鼠随机分为模型组、Tan Ⅱ A-L组(5mg/kgTan Ⅱ A灌胃)、Tan Ⅱ A-M 组(10 mg/kg Tan Ⅱ A 灌胃)和 Tan Ⅱ A-H 组(20 mg/kg Tan Ⅱ A 灌胃),每组 15 只.另随机选取 15只SD大鼠作为对照组.连续干预8周.ELISA试剂盒检测大鼠血清中肝功能相关指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素(TBIL)];HE染色和Masson染色观察大鼠肝组织病理学变化;免疫组织化学染色检测肝脏纤维化相关蛋白[转化生长因子-β1(TGF-β1)和平滑肌肌动蛋白α(α-SMA)]蛋白表达;免疫荧光检测肝星状细胞(HSC)细胞α-SMA表达强度;Western blot检测肝组织Hippo-YAP/TAZ通路相关蛋白表达.结果:与对照组比较,模型组大鼠肝组织损伤加重,血清ALT、AST、TBIL表达水平,肝组织α-SMA表达强度及 α-SMA、TGF-β1、p-YAP、p-TAZ、CTGF 蛋白水平明显增加(均 P＜0.05).与模型组比较,Tan ⅡA-L 组、Tan ⅡA-M组和Tan Ⅱ A-H组肝组织损伤减轻,血清ALT、AST、TBIL表达水平,肝组织α-SMA表达强度及α-SMA、TGF-β1、p-YAP、p-TAZ、CTGF蛋白水平明显降低(均P＜0.05),其中Tan ⅡA-H组整体效果最显著.结论:Tan ⅡA能够有效改善大鼠肝纤维化程度,抑制大鼠HSC活化,其作用机制可能与抑制Hippo-YAP/TAZ信号通路有关.
Objective:To investigate the effect of tanshinone Ⅱ A(Tan Ⅱ A)on liver fibrosis in rats with liver cirrhosis,and to analyze its potential mechanism based on the Hippo-YAP/TAZ pathway.Methods:A liver cirrhosis rat model was established by intraperitoneal injection of 40％carbon tetrachloride in peanut oil suspension.The suc-cessfully modeled rats were randomly divided into the model group,the Tan Ⅱ A-L group(intragastric administra-tion of 5 mg/kg Tan Ⅱ A),the Tan Ⅱ A-M group(intragastric administration of 10 mg/kg Tan Ⅱ A),and the TanⅡ A-H group(intragastric administration of 20 mg/kg Tan Ⅱ A),with 15 rats in each group.Another 15 SD rats were randomly selected as the control group.The intervention lasted for 8 weeks.The ELISA kits were used to detect the liver function-related indicators(ALT,AST,and TBIL)in the rat serum.HE staining and Masson staining were used to observe the pathological changes of the rat liver tissue.Immunohistochemical staining was used to detect the protein expression of liver fibrosis-related proteins(TGF-β1,α-SMA).Immunofluorescence was used to detect the expression intensity of α-SMA in HSC.Western blot was used to detect the expression of Hippo-YAP/TAZ pathway-related proteins in liver tissue.Results:Compared with the control group,the liver tissue damage in the model group was more severe,and the expression levels of serum ALT,AST,and TBIL,the expression intensity of α-SMA,and the protein levels of α-SMA,TGF-β1,p-YAP,p-TAZ,and CTGF in liver tissues were significantly increased(all P＜0.05).Compared with the model group,the liver tissue damage in the Tan Ⅱ A-L group,Tan Ⅱ A-M group,and Tan Ⅱ A-H group was alleviated,and the expression levels of serum ALT,AST,and TBIL,the expression intensity of α-SMA,and the protein levels of α-SMA,TGF-β1,p-YAP,p-TAZ,and CTGF in liver tissues were significantly de-creased(all P＜0.05).Among them,the overall effect of the Tan Ⅱ A-H group was the most significant.Conclusion:Tan Ⅱ A can effectively improve the degree of liver fibrosis in rats,inhibit the activation of HSCs,and its mechanism of action may be related to the inhibition of the Hippo-YAP/TAZ signaling pathway.
全养雅;张彩英
湖南省第二人民医院湖南省脑科医院消化内科,湖南长沙 410007湖南省第二人民医院湖南省脑科医院消化内科,湖南长沙 410007
医药卫生
肝硬化肝纤维化丹参酮ⅡA肝星状细胞Yes相关蛋白含PDZ结合基序的转录共激活因子大鼠
Liver cirrhosisLiver fibrosisTanshinone ⅡAHepatic stellate cellsYes-associated proteinTranscriptional coactivator with PDZ-binding motifRats
《陕西医学杂志》 2026 (6)
754-760,7
湖南省自然科学基金资助项目(2024JJ51192)
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