逆转素对胆管结扎诱导大鼠肝损害的影响

来源期刊：广州医药 | 9-17 发布时间：2021-11-24 收稿时间：2025/11/13 18:07:50 阅读量：92

作者：: 黄迪,

黄宇,

黄子圣,

翁杰锋,

李佩霖,

张帅,

古维立,

关键词：: 逆转素胆管结扎胆汁淤积胆管反应肝纤维化; Reversine Bile duct ligation Choletasis Ductular reaction Hepatic fibrosis

DOI：: 10.3969/j.issn.1000-8535.2021.03.002

收稿时间：: 2021-01-02
修订日期：
接收日期：
引用总数：: 0

目的探究小分子化合物逆转素(reversine,Rev)对胆管结扎(BDL)诱导的大鼠胆汁淤积性肝损害、纤维化、上皮细胞-间充质转化以及胆管反应的影响。方法雄性Lewis大鼠随机分成三组,每组各5只。按照如下处理:BDL组大鼠行2周的胆管结扎;BDL+Rev组行胆管结扎同时给予腹腔注射逆转素;对照采用假手术(Sham)。2周后获取血液和肝组织。血指标检测总白蛋白(TP)、总胆红素(TBIL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、γ谷氨酰转肽酶(GGT)。H&E染色检测肝组织病理。Azan染色检测组织胶原蛋白。免疫组化检测肝组织α平滑肌肌动蛋白(α-SMA)、结蛋白(Desmin)、波形蛋白(Vimentin)、细胞角蛋白(CK7,CK19)、β-连环蛋白(β-Catenin)以及上皮细胞粘附分子(EpCAM)蛋白的表达情况。结果胆管结扎导致肝脏合成的总白蛋白量下降,总胆红素(TBIL)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、γ谷氨酰转肽酶(GGT)水平明显上升,逆转素处理使下降的总白蛋白上升,使上升的总胆红素(TBIL)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、γ谷氨酰转肽酶(GGT)水平向正常水平回复。逆转素可以缓解胆汁淤积引起的肝纤维化,表现为下调BDL引起的胶原蛋白和α-SMA蛋白沉积。逆转素可以抑制胆汁淤积引起的上皮细胞-间充质转化表现为逆转素明显降低BDL导致的Desmin和Vimentin的表达。逆转素可以抑制胆汁淤积引起的胆管反应表现为明显减少CK7和CK19阳性胆管的表达含量。逆转素抑制胆汁淤积引起的胆管反应与调节β-Catenin和EpCAM的表达有关。结论逆转素可以缓解胆汁淤积引起的大鼠肝损害,具有一定的保护作用。逆转素可以成为一种潜在治疗药物。

Objective To investigate the effect of reversine (REV) on bile duct ligation (BDL) -induced hepatic damage, fibrosis, epithelial-mesenchymal transformation, and ductular reaction in rats. Methods Male Lewis rats were randomly divided into three groups with 5 rats in each group. Bile duct ligation was performed in the BDL group for two weeks. BDL+ REV group was treated with bile duct ligation and intraperitoneal injection of reversine. The control group was Sham operation (Sham). Blood and liver tissue were obtained after 2 weeks. Blood indexes were determined for total albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase. Hepatic histopathology was detected by H&E staining. Azan staining was used to detect tissue collagen deposition. Immunohistochemistry was used to detect the expression of α-SMA, desmin, vimentin, cytokeratin, β-catenin and epithelial cell adhesion molecule (EpCAM) protein. Results Bile duct ligation resulted in the decrease of total albumin synthesis in liver, and the increase of total bilirubin, glutamic-oxalacetic transaminase, alkaline phosphatase and γ-glutamyltranspeptidase. The levels of total bilirubin, aspartate transaminase, alkaline phosphatase and γ-glutamyltranspeptidase returned to the normal level with reversine treatment. Reversine could alleviate cholestasis-induced liver fibrosis by downregulating BDL-induced deposition of collagen and α-SMA protein. Reversine inhibited cholestasis-induced epithelial-mesenchymal transformation by significantly reducing BDL-induced desmin and vimentin expression. Reversine could inhibit cholestasis-induced ductular reaction by significantly reducing the expression of CK7 and CK19 positive biliary cells. Inhibition of cholestasis induced ductular reaction by reversine was associated with regulation of β-catenin and EpCAM expression. Conclusion Reversine can alleviate liver damage caused by cholestasis in rats and have a protective effect. Reversine may be a potential treatment that need further investigation.

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