葛根素通过抑制AHR/氧化应激途径改善酮康唑诱导的大鼠肝损伤研究  

Puerarin improves ketoconazole-induced liver injury in rats by inhibiting aromatic hydrocarbon receptors/oxidative stress pathway

作　　者：周云松 赵琦 胡芳 李叙颖 崔峻松 黄敬 黄娜娜 赵一鹏 Zhou Yunsong;Zhao Qi;Hu Fang(Department of Gastroenterology,Second Affiliated Hospital,Guizhou University of Traditional Chinese Medicine,Guiyang 550001,Guizhou Province,China)

机构地区：[1]贵州中医药大学第二附属医院消化内科,贵阳市550001 [2]贵州中医药大学研究生院,贵阳市550001 [3]贵州省兴义市人民医院

出　　处：《实用肝脏病杂志》2024年第5期669-672,共4页Journal of Practical Hepatology

基　　金：贵州省卫生健康委科研基金资助项目(编号:gzwkj2021-121)。

摘　　要：目的探讨葛根素保护酮康唑诱导的大鼠肝损伤的机制。方法将48只SD大鼠随机分为对照组、模型组、大、小剂量葛根素干预组(n=12),采用酮康唑灌胃造模或在造模的同时给予葛根素灌胃干预。采用RT-PCR法检测肝组织芳香烃受体(AHR)、细胞色素p450家族CYP1A1和CYP2E1 mRNA水平,采用免疫组化法检测肝组织AHR蛋白表达。结果模型组大鼠血清酶和氧化应激指标显著升高,提示造模成功,而葛根素干预显著降低了它们的水平(P<0.05);小剂量葛根素处理组肝组织谷胱甘肽(GSH)水平为(148.2±9.5)μM,显著高于模型组【(77.0±9.1)μM,P<0.05】,而氧化型谷胱甘肽(GSSG)水平为(84.7±9.3)μM,显著低于模型组【(131.4±13.4)μM,P<0.05】,大剂量葛根素处理组有类似的变化,只是作用更强;小剂量葛根素处理组肝组织AHR、CYP1A1和CYP2E1 mRNA相对水平分别为(28.4±3.3)、(23.7±1.8)和(9.0±1.5),均显著低于模型组【分别为(51.7±7.8)、(36.2±4.7)和(14.0±1.5),P<0.05】,大剂量葛根素组表现为作用更强;葛根素处理组动物肝组织AHR表达显著弱于模型组。结论葛根素可能通过抑制芳香烃受体介导的氧化应激反应改善酮康唑诱导的大鼠肝损伤。Objective This experiment aimed at exploring the mechanism ofprotective role of puerarin on ketoconazoleinduced liver injury in rats.Method 48 male SD rats were randomly divided into control,model,low-dose and high-dose of puerarin-intervened groups(n=12 in each).Model was established by oral ketoconazole gavage,and intervention was carried out by oral ketoconazole and low-dose and large-dose of puerarin gavage simultaneously.Hepatic tissue aromatic hydrocarbon receptors(AHR),cytochrome P4501A1(CYP1A1),and CYP2E1 mRNA levelswere assayed by RT-PCR,and hepatic expression of AHR protein was detected immunohistochemically.Results The model of liver injury was successfully established as proved enzymologically and histopathologically,and the intervention of puerarin greatly improved liver injury;hepatic tissue GSH level in low-dose puerarin-intervened group was(148.2±9.5)μM,much higher than[(77.0±9.1)μM,P<0.05],while GSSG level was(84.7±9.3)μM,much lower than[(131.4±13.4)μM,P<0.05]in the model,and in large-dose of puerarin intervention group,the changes were even more obviously;relative hepatic loads of AHR,CYP1A1 and CYP2E1 mRNA in low-dose of puerarin intervention were(28.4±3.3),(23.7±1.8)and(9.0±1.5),all significantly lower than[(51.7±7.8),(36.2±4.7)and(14.0±1.5),respectively,P<0.05]in the model,and the changes were even more obvious in large-dose of puerarin intervention;AHR expression in liver tissues with puerarin intervention was obviously weaker as compared in the model.Conclusion Puerarin could ameliorate ketoconazole-induced liver injury in rats,which might be related to inhibition of oxidative stress pathway mediated by AHR.

关 键 词：药物性肝损伤 酮康唑 葛根素 芳香烃受体 抗氧化 大鼠 

分 类 号：R575[医药卫生—消化系统]