Study on mechanism of Luhong Formula reducing myocardial ischemia⁃reperfusion injury through SLC7A11/ GPx4 signal pathway

Wan CAI; Hua ZHOU; Jijie XU; Hao CHI

doi:10.16306/j.1008-861x.2022.S1.033

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Study on mechanism of Luhong Formula reducing myocardial ischemia⁃reperfusion injury through SLC7A11/ GPx4 signal pathway

Experiment Research | 更新时间：2022-08-29

- Study on mechanism of Luhong Formula reducing myocardial ischemia⁃reperfusion injury through SLC7A11/ GPx4 signal pathway
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 36, Issue S1, Pages: 137-142(2022)
- 作者机构：
  
  1.上海中医药大学附属曙光医院心胸外科（上海　201203）
  2.上海中医药大学附属曙光医院心血管病研究所（上海　201203）
  3.上海中医药大学附属曙光医院宝山分院心血管内科（上海　201999）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2022.S1.033
  CLC：
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蔡婉,周华,徐基杰等.鹿红方通过SLC7A11/GPX4信号通路减轻心肌缺血再灌注损伤的机制研究[J].上海中医药大学学报,2022,36(S1):137-142.

CAI Wan,ZHOU Hua,XU Jijie,et al.Study on mechanism of Luhong Formula reducing myocardial ischemia⁃reperfusion injury through SLC7A11/ GPx4 signal pathway[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(S1):137-142.
蔡婉,周华,徐基杰等.鹿红方通过SLC7A11/GPX4信号通路减轻心肌缺血再灌注损伤的机制研究[J].上海中医药大学学报,2022,36(S1):137-142. DOI： 10.16306/j.1008-861x.2022.S1.033.

CAI Wan,ZHOU Hua,XU Jijie,et al.Study on mechanism of Luhong Formula reducing myocardial ischemia⁃reperfusion injury through SLC7A11/ GPx4 signal pathway[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(S1):137-142. DOI： 10.16306/j.1008-861x.2022.S1.033.

摘要

目的,2,探究鹿红方防止大鼠心肌缺血再灌注损伤（MIRI）的机制研究。,方法,2,将40只大鼠随机分为对照组、模型组、鹿红方低剂量组、鹿红方中剂量组、鹿红方高剂量组，每组8只。对照组、模型组给予0.9%NaCl溶液灌胃，鹿红方各组大鼠分别给予不同剂量的鹿红方灌胃，连续灌胃7 d，末次灌胃给药12 h，结扎左前降支30 min后复灌24 h复制大鼠缺血再灌注模型。复制模型后取材，HE染色观察心脏组织形态学变化，检测血清肌酸激酶（CK-MB）、乳酸脱氢酶（LDH）、肌钙蛋白Ⅰ（cTn-Ⅰ）、还原型谷胱甘肽（GSH）、丙二醛（MDA）和超氧化物歧化酶（SOD）含量，Western blot法检测心肌组织中非糖基化的xCT（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）蛋白表达。,结果,2,①HE染色结果显示，与对照组比较，模型组心肌细胞坏死和水肿，伴有炎性细胞浸润，鹿红方各剂量组均可改善心肌损伤，以鹿红方中、高剂量组效果最优。②相关心肌损伤标志物检测结果显示：与对照组比较，模型组CK-MB、LDH、cTn-Ⅰ和 MDA 含量明显升高（,P,<,0.05），GSH 和 SOD 含量明显下降（,P,<,0.05），鹿红方各剂量组均可不同程度降低CK-MB、LDH、cTn-Ⅰ和 MDA的含量（,P,<,0.05），升高GSH和SOD含量（,P,<,0.05），以鹿红方中、高剂量组效果最明显。③Western blot 结果显示，与模型组比较，鹿红方各剂量组均可以促进SLC7A11、GPX4蛋白表达（,P,<,0.05）。,结论,2,鹿红方可缓解心肌缺血再灌注损伤，其机制可能与上调SLC7A11/GPX4通路，进而抑制铁死亡有关。

Abstract

Objective： To explore the mechanism of Luhong Formula preventing myocardial ischemia-reperfusion injury （MIRI） in rats.,Methods,2,Forty rats were randomly divided into control group， model group， low dose group of Luhong Formula， medium dose group of Luhong Formula and high dose group of Luhong Formula， 8 in each group. The control group and the model group were given 0.9% NaCl solution by gavage， and the rats in Luhong Formula groups of different dosage were given different doses of Luhong Formula by gavage for 7 days. Twelve hours after the last gavage， the rat ischemia-reperfusion model was established by ligation of the left anterior descending branch for 30 min， and reperfusion for 24. After the model was copied， the samples were taken and the morphological changes of heart were observed by HE staining， and Serum creatine kinase （CK-MB）， lactate dehydrogenase （LDH）， troponin Ⅰ （cTn-Ⅰ）， reduced glutathione （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） were detected. The expression of non-glycosylated XCT （SLC7A11） and glutathione peroxidase 4 （GPx4） proteins in myocardial tissue were detected by Western blot.,Results,2,①HE staining showed that compared with the control group， myocardial cells in model group were necrotic and edema， accompanied by inflammatory cell infiltration. All Luhong Formula groups of different dosage could improve myocardial injury， and the effect of medium and high doses groups was the best. ②The detection results of relevant myocardial injury markers showed that compared with the control group， the concentrations of CK-MB， LDH， cTn-Ⅰ and MDA increased significantly （,P,<,0.05）， and the concentrations of GSH and SOD decreased significantly （,P,<,0.05）. Luhong Formula groups of different dosage could reduce the contents of CK-MB， LDH， cTn-Ⅰ and MDA （,P,<,0.05）， and increase the contents of GSH and SOD （,P,<,0.05）， and the effect of medium and high doses groups was the best. ③The results of Western blot showed that compared with the control group， Luhong Formula groups of different dosage could promote the expression of SLC7A11 and GPX4 protein （,P,<,0.05）.,Conclusion,2,Luhong Formula can alleviate myocardial ischemia-reperfusion injury， and its mechanism may be related to upregulating SLC7A11 / GPX4 pathway and inhibiting iron death.

关键词

鹿红方心肌缺血再灌注损伤氧化应激SLC7A11/GPX4通路铁死亡模型大鼠中药研究

Keywords

Luhong Formulamyocardial ischemia-reperfusion injuryoxidative stressSLC7A11/GPx4 pathwayiron deathmodel ratsresearch of traditional Chinese medicine

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