槲皮素对四氯化碳诱导的大鼠肝纤维化抑制作用和肝保护作用

Inhibitory and protective effects of quercetin on hepatic fibrosis induced by carbon tetrachloride in rats

目的:探讨槲皮素对四氯化碳(CCl4)诱导大鼠肝纤维化的保护作用,并阐明槲皮素的抗肝纤维化机制。方法:Wistar大鼠随机分为5组:对照组、模型组、低剂量组(EXP-L)、中剂量组(EXP-M)、高剂量组(EXP-H)。HE染色检测肝组织病理损伤情况;试剂盒检测谷丙转氨酶(ALT)和谷草转氨酶(AST)活力;羟脯氨酸(HYP)检测试剂盒检测HYP含量;ELISA检测血清炎症因子IL-6、TNF-α和IL-1β水平;Western blot检测α平滑肌肌动蛋白(α-SMA)和胶原-Ⅰ(collagen-Ⅰ)蛋白表达量;RT-PCR检测1型胶原(COL1A1)和3型胶原(COL3A1)mRNA水平。结果:槲皮素可改善CCl4诱导的肝损伤的病理表现;槲皮素可降低ALT和AST水平(P<0.01);槲皮素可减少HYP含量(P<0.01)。此外,槲皮素可减少血清炎症因子IL-6、TNF-α和IL-1β水平(P<0.01);槲皮素可抑制α-SMA和collagen-I蛋白表达以及COL1A1和COL3A1 mRNA水平(P<0.01);槲皮素可抑制Wnt信号通路β-catenin蛋白表达(P<0.01);且上述抑制作用呈剂量依赖的特征。结论:槲皮素能阻止Wistar大鼠肝纤维化的进展,且具有肝保护作用。槲皮素的抗纤维化和肝保护机制可能与Wnt信号通路有关。

Objective:To investigate the protective effect of quercetin on rat liver fibrosis induced by carbon tetrachloride(CCl4),and to elucidate the anti-fibrosis mechanism of quercetin.Methods:Wistar rats were randomly divided into 5 groups:control group,model group and low dose group(EXP-L),medium dose group(EXP-M)and high dose group(EXP-H).HE staining was used to detect the pathological damage of liver tissue.ALT and AST activity were detected with the kit.HYP content was detected by hydroxyproline(HYP)detection kit.Serum levels of inflammatory cytokines IL-6,TNF-αand IL-1βwere detected by ELISA.Western blot detection of alpha smooth muscle actin(α-SMA)and collagen-I protein expression;mRNA levels of collagen type 1(COL1A1)and collagen type 3(COL3A1)were detected by RT-PCR.Results:Quercetin could improve the pathological manifestations of liver injury induced by CCl4.Quercetin reduced ALT and AST levels(P<0.01).Quercetin could reduce HYP(P<0.01).In addition,quercetin reduced serum levels of inflammatory cytokines IL-6,TNF-αand IL-1β(P<0.01).Quercetin inhibitedα-SMA and collagen protein expression and COL1A1 and COL3A1 mRNA level(P<0.01).Quercetin could inhibit the expression ofβ-catenin protein in the Wnt signal pathway(P<0.01).The inhibitory effect was dose-dependent.Conclusion:Quercetin can prevent the progression of liver fibrosis in Wistar rats,and has a protective effect on liver.The anti-fibrosis and liver protection mechanism of quercetin may be related to the Wnt signaling pathway.