活血清解灵通过调控Sirt1-自噬信号通路减轻胆管结扎诱导的大鼠肝纤维化OA
Huoxue Qingjie Ling alleviates bile duct ligation-induced hepatic fibrosis in rats by regulating the Sirt1-autophagy signaling pathway
目的 探讨活血清解灵(HXQJL)通过调控沉默信息调节因子1(Sirt1)信号通路介导的自噬改善胆管结扎(BDL)诱导的肝纤维化.方法 采用BDL处理SD大鼠,并随机分为:假手术组(Sham)、模型组(BDL)、活血清解灵低、高剂量组(HXQJL-L、HXQJL-H),Sirt1抑制剂Ex527组(EX527),活血清解灵联合Ex527组(HXQJL+EX527).HE和天狼星红染色观察肝组织病变和胶原沉积变化;生化检测血清ALT、AST、ALP和GGT水平.RT-PCR 和Western blotting法分别检测α-SMA、FN、COL I、Atg 5、Beclin1、p62、LC3B和Sirt1 的表达.免疫荧光检测α-SMA、LC3B和Sirt1的表达.结果 与Sham组比较,BDL组肝细胞损伤、炎细胞浸润及胶原沉积面积增多(P<0.05),血清中ALT、AST、ALP、GGT水平增加(P<0.05).同时肝组织中α-SMA、FN、COL I、Atg 5和Beclin1表达增加,LC3B-II/I比值增加(P<0.05),而p62和Sirt1表达降低(P<0.05).与BDL组相比,活血清解灵各剂量组肝细胞损伤、炎细胞浸润及胶原沉积面积减少(P<0.05),ALT、AST、TBA、ALP水平降低(P<0.05),肝组织中α-SMA、FN、COL I、Atg 5和Beclin1表达降低(P<0.05),LC3B-II/I比值降低,而p62和Sirt1表达增加(P<0.05);而Ex527组肝细胞损伤、炎细胞浸润及胶原沉积面积增多(P<0.05),ALT、AST、TBA、ALP水平升高(P<0.05),肝组织中α-SMA、FN、COL I、Atg 5和Beclin1表达升高,LC3B-II/I比值升高(P<0.05),而p62和Sirt1表达降低(P<0.05).与HXQJL-H组相比,Ex527可以阻断活血清解灵对大鼠肝组织损伤、肝功能、肝纤维化和自噬的作用.结论 活血清解灵通过调控Sirt1-自噬信号通路对胆管结扎诱导肝纤维化具有保护作用.
Objective To investigate the protective effect of Huoxue Qingjie Ling(HXQJL)agaisnt bile duct ligation(BDL)-induced liver fibrosis in rats and the underlying mechanism.Methods SD rats were randomized into sham-operated group,BDL model group,low-and high-dose HXQJL treatment groups,Ex527(a Sirt1 inhibitor)group(EX527),and HXQJL+Ex527 group.Liver histopathological changes and collagen deposition were observed using HE and Sirius Red staining,and serum levels of ALT,AST,ALP,and GGT of the rats were measured using biochemical assays.The expression levels of α-SMA,FN,COL I,Atg5,Beclin1,p62,LC3B,and Sirt1 were determined by RT-PCR and Western blotting.Immunofluorescence staining was used to detect the expression of α-SMA,LC3B,and Sirt1.Results Compared with the sham-operated rats,the rats in BDL model group exhibited increased hepatocyte injury,inflammatory cell infiltration,and collagen deposition area with elevated serum levels of ALT,AST,ALP,and GGT,enhanced haptic expressions of α-SMA,FN,COL I,Atg5,and Beclin1,an increased LC3B-II/I ratio,and lowered hepatic expressions of p62 and Sirt1.All these changes were significantly alleviated in the two HXQJL treatment groups but aggravated in EX527 treatment group.Compared with those in high-dose HXQJL group,the protective effects of HXQJL on liver tissue injury,liver function,liver fibrosis,and autophagy were obviously mitigated by treatment with Ex527.Conclusion HXQJL has protective effect against BDL-induced liver fibrosis in rats by modulating the Sirt1-autophagy signaling pathway.
李彩霞;崔立华;曹婕;樊宇星;周雪颖;张淑坤;左艳洁
天津医科大学附属南开医院天津市急腹症器官损伤与中西医修复重点实验室,天津 300100天津医科大学附属南开医院天津市急腹症器官损伤与中西医修复重点实验室,天津 300100天津医科大学研究生院,天津 300100天津医科大学研究生院,天津 300100天津中医药大学南开临床学院超声科,天津 300100天津医科大学附属南开医院天津市急腹症器官损伤与中西医修复重点实验室,天津 300100天津中医药大学南开临床学院超声科,天津 300100
活血清解灵肝纤维化自噬Sirt1EX527
Huoxue Qingjie Linghepatic fibrosisautophagySirt1EX527
《南方医科大学学报》 2026 (3)
513-522,10
天津市卫生健康委中医中西医结合重点项目(2023046)
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