加味二至丸通过抑制铁死亡减轻高脂血症小鼠肝脏脂质沉积  

Jiawei-Erzhi pills attenuate liver lipid deposition in mice with hyperlipidemia by inhibiting ferroptosis

作　　者：马贵萍 于忠杨 卿立金[1] 李俊龙 洪创雄[1,2] MA Gui-ping;YU Zhong-yang;QING Li-jin;LI Jun-long;HONG Chuang-xiong(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The First Clini-cal Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Lingnan Medical Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Qingdao Sixth People's Hospital,Qingdao 266033,China)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405 [2]广州中医药大学第一临床医学院,广东广州510405 [3]广州中医药大学岭南医学研究中心,广东广州510405 [4]青岛市第六人民医院,山东青岛266033

出　　处：《中国病理生理杂志》2022年第2期259-266,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金项目(No.81373799);广东省中医药强省建设指标体系构建研究(No.20173004)。

摘　　要：目的:观察加味二至丸对高脂血症模型小鼠肝脏脂质沉积及铁死亡相关蛋白表达的影响。方法:30只ApoE-/-小鼠随机分为模型组、辛伐他汀组和加味二至丸组,每组10只,另取10只相同背景的C57BL/6J小鼠作为正常对照组。模型组及各治疗组均给予高脂饲料喂养,正常对照组给予普通饲料喂养。造模12周后按分组分别给予相应的药物灌胃,正常对照组和模型组给予等体积的生理盐水灌胃。药物干预10周以后取小鼠血清及肝组织,全自动生化分析仪检测血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的含量;HE染色和油红O染色观察小鼠肝组织形态及脂质沉积;试剂盒检测肝组织及血清中还原型谷胱甘肽(GSH)水平及肝组织中的铁含量;RT-qPCR及Western blot检测肝组织中铁死亡相关因子GPx4、SLC7A11、p53、NOX1、COX2和FTH1的mRNA及蛋白表达。结果:与模型组相比,加味二至丸组小鼠血清TC、TG和LDL-C明显降低,HDL-C含量明显升高(P<0.05);血清及肝组织GSH水平明显升高(P<0.05),肝脏铁沉积明显缓解(P<0.05);肝组织脂滴变小且脂肪变性程度明显减轻;加味二至丸组小鼠肝组织p53、COX2和NOX1的mRNA及蛋白表达水平明显下降(P<0.05),SCL7A11、GPx4和FTH1的mRNA及蛋白表达水平明显升高(P<0.05)。结论:加味二至丸可以减轻高脂血症模型小鼠肝脏脂质沉积,可能与抑制肝脏铁死亡途径相关。AIM:To observe the effects of Jiawei-Erzhi pills on liver lipid deposition and ferroptosis-related protein expression in mice with hyperlipidemia.METHODS:Thirty ApoE-/-mice fed with high-fat diet were randomly divided into model,simvastatin,and Jiawei-Erzhi pill groups,with 10 mice in each group. Ten C57 BL/6 J mice served as normal control group. The corresponding drugs were given intragastrically. The mice in normal control group and model group were given the same volume of normal saline for 10 weeks. The automatic biochemical analyzer was used to measure serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)content. HE staining and oil red O staining were applied to observe the morphological changes and lipid deposition of mouse liver tissues. The levels of reduced glutathione(GSH)in liver tissue and serum and iron content in liver tissue were measured by kits. The expression levels of ferroptosis-related factors GPx4,SLC7 A11,p53,NOX1,COX2 and FTH1 in liver tissue were detected by RT-qPCR and Western blot.RESULTS:Jiawei-Erzhi pills significantly reduced serum TC,TG and LDL-C,increased the content of HDL-C and GSH(P<0. 05),and reduced liver iron deposition and lipid droplets. Down-regulation of p53,COX2 and NOX1 mRNA and protein levels(P<0. 05),and increased SCL7 A11,GPx4 and FTH1 levels were observed in Jiawei-Erzhi pill group(P<0. 05).CONCLUSION:JiaweiErzhi pills reduce liver lipid deposition in mice with hyperlipidemia by inhibiting liver ferroptosis pathway.

关 键 词：加味二至丸 高脂血症 铁死亡 肝脏脂质沉积 小鼠 

分 类 号：R589.2[医药卫生—内分泌] R363.2[医药卫生—内科学]