槐耳颗粒缓解奥沙利铂诱导肝脏损伤的作用及机制研究  

Study on the effect and mechanism of Huaier granules in relieving oxaliplatin-induced liver injury

作　　者：朱晨 张程亮 杨金玉 兰露露 李国栋 李敏[1] 刘东[1] 任秀华[1] ZHU Chen;ZHANG Cheng-liang;YANG Jin-yu;LAN Lu-lu;LI Guo-dong;LI Min;LIU Dong;REN Xiu-hua(Department of Pharmacy,Affiliated Tongji Hospital,Tongji Medical College,Huazhong University of Science&Technology,Hubei Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,湖北武汉430030

出　　处：《中国医院药学杂志》2021年第17期1723-1729,共7页Chinese Journal of Hospital Pharmacy

基　　金：湖北省药品(医疗器械)不良反应监测中心课题(编号:20160422);华中科技大学同济医学院研究型临床医师资助计划(编号:5001540076);中国毒理学会临床毒理专项研究课题(编号:CST2020CT107)。

摘　　要：目的:探究槐耳颗粒对奥沙利铂(OXA)诱导的肝脏损伤的保护作用及内在机制。方法:采用70只雄性C57BL/6小鼠,随机分为7组,分别为正常对照组,模型对照组,药物对照组,槐耳低、中、高剂量组及阳性对照组。除正常对照组和药物对照组给予等体积的5%葡萄糖溶液外,其余各组腹腔注射(i.p)10 mg·kg^(-1) OXA溶液造模,每周一次,共6周。每周给予OXA造模的同时,槐耳不同剂量组分别灌胃(ig.)给予2、4、8 mg·g^(-1)的槐耳颗粒溶液,阳性对照组给予1.3 mg·g^(-1)的N-乙酰半胱氨酸(i.p),每日一次。药物对照组给予8 mg·g^(-1)的槐耳颗粒溶液(ig.),正常和模型对照组则给予0.9%的氯化钠溶液(ig.),连续42日。造模及给药结束后,取小鼠血清及肝脏组织,分别检测血清天门冬酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(AKP)和肝脏丙二醛(MDA)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)及过氧化氢酶(CAT)水平;称体重、肝重,计算肝重比;HE染色观察肝脏组织病理学变化。Western blot法检测肝脏氧化应激通路PI3K、P-AKT、Nrf2、HO-1、NQO1、GCLM、GCLC的蛋白表达变化,并分析PI3K两种亚型PI3K p85、PI3K p110的变化。结果:槐耳颗粒能显著降低模型组小鼠肝重/体重的值,降低血清AST、ALT和肝脏MDA水平,升高肝脏SOD、GSH水平(P<0.05);显著上调PI3K、P-AKT、Nrf2、HO-1、NQO1、GCLM和GCLC蛋白表达(P<0.05),且槐耳颗粒对PI3K p85和PI3K p110两种亚型均有上调作用。结论:槐耳颗粒可以缓解OXA诱导的肝脏损伤情况,其作用机制可能与通过PI3K/Akt/Nrf2信号通路调控氧化还原平衡有关。OBJECTIVE To explore the protective effect and mechanism of Huaier granule on oxaliplatin(OXA)-induced liver injury.METHODS A total of 70 male C57 BL/6 mice were randomly divided into 7 groups of normal,model,drug control,low/medium/high-dose Huaier and positive control(n=10 each).Except normal and drug control groups receiving an equal volume of 5%glucose solution,the other groups were intraperitoneally injected with 10 mg·kg^(-1) OXA solution for modeling once a week for 6 weeks.At the same time that OXA was given weekly for modeling,different dose groups of huaier received an intragastric gavage of 2,4,8 mg·g^(-1) Huaier granule solution and positive control group received an intraperitoneal injection of 1.3 mg·g^(-1) N-acetylcysteine once daily.Drug control group received 8 mg·g^(-1) Huaier granule solution while normal and model groups 0.9%sodium chloride solution for 42 days.Then sera and liver tissues were harvested for detecting the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(AKP)in sera and malondialdehyde(MDA),superoxide dismutase(SOD),reduced glutathione(GSH)and catalase(CAT)in liver;body and liver weights were measured and liver weight ratio was calculated.The histopathological changes of liver were observed by staining.The protein expressions of PI3 K,P-AKT,Nrf2,HO-1,NQO1,GCLM and GCLC were detected by Western blot and the changes of PI3 K p85 and PI3 K P110 were analyzed.RESULTS Huaier granule could significantly lower the ratio of liver weight/body weight,decrease the serum levels of AST,ALT and MDA and the hepatic levels of SOD and GSH(P<0.05)and significantly up-regulated the protein expressions of PI3 K,P-AKT,Nrf2,HO-1,NQO1,GCLM and GCLC(P<0.05).Moreover,Huaier granule could up-regulate the subtypes of PI3 K p85 and PI3 K p110.CONCLUSION Huaier granule can alleviate OXA-induced liver injury.And its mechanism may be correlated with regulating redox balance through the PI3 K/Akt/Nrf2 signaling pathway.

关 键 词：槐耳颗粒 奥沙利铂 肝损伤 氧化应激 PI3K NRF2 

分 类 号：R96[医药卫生—药理学]