谷胱甘肽通过Nrf2/ARE通路改善四氯化碳诱导大鼠肝损伤和肝纤维化

Reduced glutathione improves liver injury and liver fibrosis induced by carbon tetrachloride in rats through Nrf2/ARE pathway

目的探讨谷胱甘肽(GSH)对四氯化碳(CCl4)诱导的大鼠肝损伤和肝纤维化的疗效和保护机制。方法利用CCl4处理雄性SD大鼠,分别给予生理盐水和谷胱甘肽治疗。收集大鼠血液以测量生化指标(ALT、AST、ALP)和炎症因子(IL-6、TNF-a和IL-1β),收集肝脏组织进行组织病理学分析、纤维化标志蛋白、促纤维化信号分子、Nrf2/ARE通路相关蛋白的表达分析。结果谷胱甘肽改善了CCl4诱导的肝损伤,降低了炎症因子的表达。谷胱甘肽还通过减少纤维化标志蛋白和促纤维化信号分子的表达,以及降低脂质过氧化物和丙二醛的水平和提高谷胱甘肽含量来改善肝脏氧化应激。此外,谷胱甘肽可以激活Nrf2/ARE通路,提高Nrf2下游抗氧化基因的表达,减轻CCl4诱导的大鼠肝脏氧化应激。结论谷胱甘肽在体内保护大鼠肝脏免受CCl4引起的损伤和纤维化,这与抑制HSC活化和减轻氧化应激有关。

Objective The aim of this study was to investigate the effect and protective mechanism of reduced glutathione on liver injury and fibrosis induced by carbon tetrachloride(CCl4)in rats.Methods Male Sprague-Dawley(SD)rats were treated with CCl4 and given normal saline and protoglutathione respectively.Biochemical indexes(ALT,AST,ALP)and inflammatory factors(IL-6,TNF-a,and IL-1β)were measured in the blood of rats.Histopathological analysis,expression of fibrosis marker proteins,pro-fibrosis signaling molecules,and Nrf2/ARE pathway related proteins were performed in liver tissues.Results Glutathione improved CCL4-induced liver injury and decreased the expression of inflammatory factors.Glutathione also ameliorates hepatic oxidative stress by reducing the expression of fibrotic marker proteins and pro-fibrotic signaling molecules,as well as reducing lipid peroxides and malondialdehyde levels and increasing glutathione content.In addition,glutathione can activate the Nrf2/ARE pathway,increase the expression of Nrf2 downstream antioxidant genes,and alleviate CCL4-induced oxidative stress in rat liver.Conclusion Glutathione in vivo protects the rat liver from CCL4-induced damage and fibrosis,which is associated with inhibiting HSC activation and alleviating oxidative stress.