瘀血痹含药血清通过DJ-1/GPX4抑制心肌细胞铁死亡的作用机制  

Study on Mechanism of Yuxuebi Capsule( 瘀血痹胶囊) - containing Serum Inhibiting Ferroptosis on Myocardial Cell through DJ - 1 /GPX4

作　　者：黄国威[1] 于游[1] 张欢[1] 庞琳琳[1] 赵宏月[1] 陈韦[1] 周鑫[1] 于睿[1] HUANG Guowei;YU You;ZHANG Huan;PANG Linlin;ZHAO Hongyue;CHEN Wei;ZHOU Xin;YU Rui(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847

出　　处：《中华中医药学刊》2022年第6期126-129,I0039,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81774022);辽宁省自然科学基金指导计划(20180550767);辽宁省科学技术计划项目工业重大专项(2020JH1/10100022);辽宁省“兴辽英才计划”项目(XLYC1802004);辽宁省教育厅科学技术研究项目(L201948)。

摘　　要：目的探讨瘀血痹含药血清对心肌HL-1细胞铁死亡的影响及对DJ-1/谷胱甘肽过氧化物酶4(GPX4)信号通路的作用机制。方法将SD大鼠随机分为正常组、瘀血痹含药血清低剂量组(0.1 g/kg)、中剂量组(0.2 g/kg)、高剂量组(0.4 g/kg),正常组生理盐水灌胃,并制备含药血清。HL-1心肌细胞分为:正常组,模型组,瘀血痹含药血清低、中、高剂量组。各组细胞按相应剂量药物处理并培养24 h后,检测各组HL-1细胞活性氧(reactive oxygen species,ROS)水平、丙二醛(MDA)、总超氧化物歧化酶(T-SOD)、还原型谷胱甘肽(GSH)水平,Western Blot法检测各组HL-1细胞DJ-1、p53、GPX4和重组人铁蛋白重链(FTH1)蛋白表达水平,RT-PCR检测各组HL-1细胞心房钠尿肽(ANP)和B型利钠肽(BNP mRNA)水平。结果与正常组比较,模型组HL-1细胞ROS、MDA、ANP和BNP mRNA以及p53蛋白表达显著升高(P<0.01),T-SOD、GSH、DJ-1、GPX4和FTH1蛋白表达水平显著降低(P<0.01)。与模型组比较,瘀血痹含药血清低、中、高剂量组HL-1细胞ROS、MDA,ANP和BNP mRNA以及p53蛋白表达显著降低(P<0.01),T-SOD、GSH、DJ-1、GPX4和FTH1蛋白表达水平显著升高(P<0.01)。结论瘀血痹含药可能通过激活DJ-1/GPX4信号通路抑制心肌细胞铁死亡,改善心肌肥大,具有抗心力衰竭的作用。Objective To explore the protective mechanism of Yuxuebi Capsule(瘀血痹胶囊)-containing serum on ferropto-sis of HL-1 cells and the mechanism of the DJ-1/glutathione peroxidase 4(GPX4)signaling pathway.Methods Forty SD rats were randomly divided into 4 groups:normal group,low,medium and high dose of Yuxuebi Capsule-containing serum groups(0.1,0.2,0.4 g/kg).The normal group was given intragastric administration of normal saline.The Yuxuebi Capsule-contai-ning serum was prepared.HL-1 cells were divided into normal group,model group and low,medium and high dose of Yuxuebi Capsule-containing serum groups.After the cells of each group were treated with the corresponding doses of drugs and cultured for 24 hours,the levels of reactive oxygen species(ROS),malondialdehyde(MDA),total superoxide dismutase(T-SOD)and re-duced glutathione(GSH)in HL-1 cells of each group were detected,the expression levels of DJ-1,p53,GPx4 and FTH1 pro-teins in HL-1 cells of each group were detected by Western Blot,and the mRNA levels of ANP and BNP in HL-1 cells of each group were detected by RT-PCR.Results Compared with those of the normal group,the expressions of ROS,MDA,ANP,BNP mRNA and p53 protein in HL-1 cells in the model group were significantly increased(P<0.01),and the expressions of T-SOD,GSH,DJ-1,GPx4 and FTH1 protein were significantly decreased(P<0.01).Compared with those of the model group,the expressions of ROS,MDA,ANP,BNP mRNA and p53 protein in HL-1 cells in the low,medium and high dose of Yuxuebi Capsule-containing serum groups were significantly decreased(P<0.01),and the expressions of T-SOD,GSH,DJ-1,GPx4 and FTH1 protein were significantly increased(P<0.01).Conclusion Yuxuebi Capsule-containing serum may inhibit the fer-roptosis of cardiomyocytes and improve myocardial hypertrophy by activating DJ-/GPx4 signal pathway,and plays an anti-heart failure role.

关 键 词：心力衰竭 心肌细胞 铁死亡 瘀血痹胶囊 DJ-1/GPX4 

分 类 号：R285.5[医药卫生—中药学]