健肝乐对异烟肼和利福平联用致肝损伤大鼠的保护作用及对Nrf-2/HO-1/NF-κB通路的影响  

Protective effect of Jianganle on liver injury induced by isoniazid and rifampicin and its effect on Nrf-2/HO-1/NF-κB pathway in rats

作　　者：马丽华 张欢 丁巧燕 张宇 李思思 王飞 李星逸 周铭 MA Li-hua;ZHANG Huan;DING Qiao-yan;ZHANG Yu;LI Si-si;WANG Fei;LI Xing-yi;ZHOU Ming(Department of Pharmacy,Wuhan Pulmonary Hospital,Wuhan 430030;Pharmacology Group,Suizhou Zengdu Hospital,Suizhou Vocational and Technical College,Suizhou 441399,China)

机构地区：[1]武汉市肺科医院药学部,湖北武汉430030 [2]随州市曾都医院、随州市职业技术学院护理学院药理组,湖北随州441399

出　　处：《解剖科学进展》2024年第3期263-266,共4页Progress of Anatomical Sciences

基　　金：武汉市卫生健康委科研项目(WX21Z04)。

摘　　要：目的探究健肝乐对异烟肼(INH)和利福平(RFP)联用所致肝损伤大鼠肝组织核因子E2相关因子(Nrf2)/血红素氧合酶1(HO-1)/核因子κB(NF-κB)通路的影响。方法60只SPF级雄性SD大鼠随机分为对照组、模型组、低剂量健肝乐组和高剂量健肝乐组,灌胃给予INH和RFP(150 mg/kg)建立肝损伤模型。给药结束后,计算肝脏脏器系数(LI);HE染色观察大鼠肝组织形态;检测大鼠血清氧化应激与炎症指标水平;免疫荧光检测大鼠肝组织NF-κB的核移位;Western blot检测大鼠肝组织Nrf-2、HO-1和NF-κB p65的表达。结果健肝乐低、高剂量处理后,肝损伤大鼠肝脏LI及血清中ALT、AST、ALP水平、SOD、GSH-Px活性、GSH含量、IL-1β、IL-6、TNF-α水平及Nrf2、HO-1蛋白表达明显降低,NF-κB核移位荧光强度明显减弱,肝组织中MDA水平及NF-κB p65蛋白表达明显升高(P<0.05),且呈剂量依赖性。结论健肝乐可通过调控Nrf2/HO-1/NF-κB信号通路减轻异烟肼和利福平所致的肝损伤。Objective To explore the effect of Jianganle on nuclear factor E2 related factor(Nrf2)/heme oxygenase 1(HO-1)/nuclear factor kappa B(NF-κB)pathway in liver tissue of rats with liver injury induced by isoniazid(INH)and rifampicin(RFP).Methods 60 SPF male SD rats were randomly divided into control group,model group,low dose Jianganle group and high dose Jianganle group.INH and RFP(150 mg/kg)were given by gavage to establish a liver injury model.Liver organ coefficient(LI)was calculated after administration.The liver morphology was observed by HE staining.The levels of oxidative stress and inflammation in serum were detected.Nuclear translocation of NF-κB in liver of rats was detected by immunofluorescence.The expressions of Nrf-2,HO-1 and NF-κB p65 in liver of rats were detected by Western blot.Results The levels of ALT,AST,ALP,activity of SOD and GSH-PX,content of GSH,levels of IL-1β,IL-6,TNF-α,and the expressions of Nrf2,HO-1 in liver and serum of liver injured rats were significantly decreased after treatment with low and high doses of Jianganle,and the fluorescence intensity of NF-κB nuclear translocation was significantly decreased.The level of MDA and the expression of NF-κB p65 protein in liver tissue were significantly increased(P<0.05)in a dose-dependent manner.Conclusion Jianganle can reduce liver injury induced by isoniazid and rifampicin by regulating the Nrf2/HO-1/NF-κB signaling pathway.

关 键 词：健肝乐 肝损伤 氧化应激 炎症反应 

分 类 号：R521[医药卫生—内科学]