机构地区:[1]浙江中医药大学第三临床医学院,杭州310000
出 处:《重庆医学》2020年第10期1570-1574,1584,共6页Chongqing medicine
基 金:2017年浙江省医药卫生计划项目(2017KY519)。
摘 要:目的探讨滨蒿内酯对胆总管结扎大鼠法尼醇X受体(FXR)/胆盐输出泵(BSEP)信号通路及肝内胆汁淤积的影响。方法 SD大鼠随机分为假手术组、模型组、滨蒿内酯低剂量组(25mg/kg)、滨蒿内酯中剂量组(50mg/kg)、滨蒿内酯高剂量组(100mg/kg)、熊去氧胆酸组(60mg/kg),每组12只,除假手术组外,其余各组大鼠结扎胆总管建立肝内胆汁淤积模型,分组给予相应药物处理后,检测肝功能指标血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平、总胆红素(TBIL)、直接胆红素(DBIL)水平;以苏木素-伊红(HE)检测各组大鼠肝组织病理变化;以Masson染色检测大鼠肝组织纤维化程度;以酶联免疫吸附试验(ELISA)试剂盒检测大鼠血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)及转化生长因子β1(TGF-β1)水平,以Western blot检测肝组织中FXR/BSEP通路蛋白表达。结果与假手术组相比,模型组大鼠肝组织呈现肝索排列紊乱,肝小叶结构受损,肝细胞坏死,有大量炎症细胞浸润等病理损伤,且出现大量胶原沉积,呈现纤维化变性,血清ALT、AST、TBIL、DBIL、TNF-α、TGF-β1及IL-6水平明显升高(P<0.05),肝组织FXR、BSEP蛋白表达明显降低(P<0.05)。与模型组相比,滨蒿内酯低、中、高剂量组、熊去氧胆酸组大鼠肝组织病理损伤及纤维化程度减轻,血清ALT、AST、TBIL、DBIL、TNF-α、TGF-β1及IL-6水平降低(P<0.05),肝组织FXR、BSEP蛋白表达升高(P<0.05),滨蒿内酯各剂量组呈剂量依赖性,滨蒿内酯高剂量组与熊去氧胆酸组相比,差异无统计学意义(P>0.05)。结论滨蒿内酯可阻止胆总管结扎大鼠肝组织炎症发生,缓解其纤维化进展,改善肝内胆汁淤积症状,增强肝功能,可能是通过FXR/BSEP通路实现的。Objective To investigate the effect of Scoparone on the signaling pathway of farnesoid X receptor(FXR)/bile salt export pump(BSEP)and intrahepatic cholestasis in rats with common bile duct ligation.Methods SD rats were randomly divided into the sham group,the model group,the low-dose Scoparone group(25 mg/kg),the medium-dose Scoparone group(50 mg/kg),the high-dose Scoparone group(100 mg/kg),the ursodeoxycholic acid group(60 mg/kg),with 12 rats in each group.Except for the sham group,rats in other groups were ligated to establish intrahepatic cholestasis model,the rats were treated with corresponding drugs.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),and direct bilirubin(DBIL)were measured.Hematoxylin eosin staining(HE)was used to detect the pathological changes of liver tissue.The degree of hepatic fibrosis was detected by Masson staining.The levels of TNF-α,IL-6 and TGF-β1 in serum of rats were detected by ELISA,and the expression of FXR/BSEP pathway protein in liver tissue was detected by Western blot.Results Compared with the sham group,the liver tissue of the model group showed disorder of liver cord arrangement,damage of liver lobule structure,necrosis of liver cells,infiltration of a large number of inflammatory cells and other pathological damage,and a large number of collagen deposition,fibrosis and degeneration,the levels of serum ALT,AST,TBIL,DBIL,TNF-α,TGF-β1 and IL-6 significantly increased(P<0.05),and the expressions of FXR,BSEP proteins in liver tissue decreased significantly(P<0.05).Compared with the model group,the pathological damage and fibrosis degree of the liver tissue in the low,middle and high dose groups of Scoparone and the ursodeoxycholic acid group were reduced.The levels of serum ALT,AST,TBIL,DBIL,TNF-α,TGF-β1 and IL-6 decreased(P<0.05),and the expressions of FXR,BSEP proteins in liver tissue increased(P<0.05).Each dose group of Scoparone was dose-dependent,and there was no significant difference between the high dose gro
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