清热袪浊胶囊通过抑制铁死亡治疗非酒精性脂肪肝炎的作用机制  

The mechanism of Qingre Quzhuo capsule in the treatment of non⁃alcoholic steatohepatitis by inhibiting ferroptosis

作　　者：李华君[1] 吕树泉[1] 王立新[1] 刘爱茹[1] 王亚男 苏秀海[1] 王元松[1] LI Hua-jun;LV Shu-quan;WANG Li-xin;LIU Ai-ru;WANG Ya-nan;SU Xiu-hai;WANG Yuan-song(CangZhou Hospital of Integrated Traditional Chinese and Western Medicine,Cangzhou 314000,China)

机构地区：[1]河北省沧州中西医结合医院,河北沧州314000

出　　处：《海南医学院学报》2023年第21期1620-1624,1631,共6页Journal of Hainan Medical University

基　　金：苏秀海全国名老中医药专家传承工作室[国中医药人教函(2022)75号]。

摘　　要：目的:探究清热袪浊胶囊(QRQZ)治疗非酒精性脂肪肝炎(NASH)的效果并从抑制铁死亡的角度探究其作用机制。方法:60只C57BL/6J小鼠适应性喂养1周后随机分为正常(Control)、模型(Model)、铁死亡抑制剂(Fer-1,10mg/kg,灌胃)、低剂量QRQZ(QRQZL,482mg/kg,灌胃)、中剂量QRQZ(QRQZM,964 mg/kg,灌胃)、高剂量QRQZ(QRQZH,1929 mg/kg,灌胃)6组,每组10只。正常组给予正常饮食,另外5组实验组均给予胆碱缺乏(MCD)饮食。整个给药过程持续6周,每周统计小鼠体重,6周后采集小鼠血液,分离血清测定ALT与AST,采集小鼠肝脏称重后固定,取同一部位进行HE与油红O染色,观察肝组织病理学变化,采用试剂盒测定肝组织中TC、TG、总铁、GSH、GSSG水平,采用RT-qPCR检测Gpx4 mRNA表达,采用Western blotting检测FTH1、FTL、GPX4蛋白表达。结果:与模型组相比,Fer-1与QRQZ治疗后,NASH小鼠体重与肝指数有所回升,肝组织病变得到不同程度的缓解,TC、TG、ALT、AST都有不同程度的好转,肝组织Fe水平明显下降,FTH1、FTL蛋白相对水平明显升高,GSH/GSSG明显上升,Gpx4 mRNA以及GPX4蛋白的表达水平明显升高。结论:QRQZ可以通过促进GSH/GPX4抗氧化系统的表达以及抑制铁死亡缓解NASH小鼠的肝损伤。Objective:To explore the effect of Qingre Quzhuo Capsule(QRQZ)in the treatment of non⁃alcoholic steato⁃hepatitis(NASH)and to explore its mechanism from the perspective of inhibiting ferroptosis.Methods:60 C57BL/6J mice were randomly divided into 6 groups:Control,model,ferroptosis inhibitor(Fer⁃1,10 mg/kg,gavage),low⁃dose QRQZ(QRQZL,482 mg/kg,gavage),medium⁃dose QRQZ(QRQZM,964 mg/kg,gavage),and high⁃dose QRQZ(QRQZH,1929 mg/kg,gavage).The control group was given normal diet,and the other experimental groups were given MCD diet.The whole adminis⁃tration process lasted for 6 weeks.The body weight of mice was counted every week.After 6 weeks,the blood of mice was collect⁃ed,and the serum was separated to determine ALT and AST.The liver of mice was weighed and fixed.The same part was stained with HE and Oil Red O to observe the pathological changes of liver tissue.The levels of TC,TG,total iron,GSH and GSSG in liver tissue were measured by kit.The expression of Gpx4 mRNA was detected by RT⁃qPCR,and the expression of FTH1,FTL and GPX4 protein was detected by Western blotting.Results:Compared with the model group,after treatment with Fer⁃1 and QRQZ,the body weight and liver index of NASH mice increased,the liver tissue lesions were alleviated,TC,TG,ALT and AST were improved,the liver tissue iron level decreased significantly,the relative levels of FTH1 and FTL proteins in⁃creased significantly,GSH/GSSG increased significantly,and the expression of Gpx4 mRNA and GPX4 protein increased signifi⁃cantly.Conclusion:QRQZ alleviates liver injury in NASH mice by promoting the expression of GSH/GPX4 antioxidant system and inhibiting ferroptosis.

关 键 词：非酒精性脂肪肝炎 清热袪浊胶囊 铁死亡 GPX4 抗氧化 

分 类 号：R285[医药卫生—中药学]