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Protective Effect of Pravastatin on Myocardial Ischemia Reperfusion Injury by Regulation of the miR-93/Nrf2/ARE Signal Pathway
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-09-22 , DOI: 10.2147/dddt.s251726 Zhiqiang Liu 1 , Fucheng Zhang 1 , Lipei Zhao 1 , Xueping Zhang 1 , Yibo Li 1 , Lingling Liu 1
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-09-22 , DOI: 10.2147/dddt.s251726 Zhiqiang Liu 1 , Fucheng Zhang 1 , Lipei Zhao 1 , Xueping Zhang 1 , Yibo Li 1 , Lingling Liu 1
Affiliation
Purpose: This research intended to study the mechanism of pravastatin in myocardial ischemia reperfusion (I/R) injury.
Patients and Methods: Altogether 70 male rats were selected and grouped into Sham operation group (Sham group), ischemia reperfusion group (I/R group), pravastatin pretreatment group (I/R+P group), I/R+miR-93-mimics, I/R+P+miR-93-mimics, I/R+Nrf2 siRNA, and I/R+P+Nrf2 siRNA group. The myocardial function of each group was detected.
Results: Myocardial I/R injury could lead to abnormal myocardial enzyme activity, inflammatory reaction and oxidative stress. However, pravastatin could significantly inhibit the activity of myocardial enzymes, alleviate inflammatory reaction and inhibit oxidative stress reaction, thus playing a protective role. Furthermore, cell experiments showed that pravastatin can alleviate the injury of H9C2 myocardial cells caused by I/R, inhibit the apoptosis of myocardial cells, and lead to a significant reduction in pro-apoptotic genes Bax, caspase-3 and caspase-9 transcription levels, an obvious increase in anti-apoptotic gene Bcl-2, and an increase in cell activity. After I/R induced injury, miR-93 level was significantly up-regulated and Nrf2 level was down-regulated. Over-expression of miR-93 or inhibition of Nrf2 expression would lead to further aggravation of I/R myocardial injury, increase the apoptosis rate of cells and decrease the activity of myocardial cells. Pravastatin administration could inhibit miR-93, activate and promote Nrf2 in myocardial tissue, and promote protein expression of downstream regulatory genes HO-1 and NQO1. In the I/R model, pravastatin was given. Over-expression of miR-93 or silencing Nrf2 could reverse the therapeutic effect of pravastatin on I/R.
Conclusion: Pravastatin acts as a protector on myocardial ischemia reperfusion injury by regulating miR-93/Nrf2/ARE signaling pathway.
Keywords: pravastatin, miR-93/Nrf2/ARE, myocardial ischemia reperfusion injury, protective effect
中文翻译：
普伐他汀通过调控miR-93/Nrf2/ARE信号通路对心肌缺血再灌注损伤的保护作用
目的：本研究旨在研究普伐他汀在心肌缺血再灌注（I/R）损伤中的作用机制。
患者与方法：共选取雄性大鼠70只，分为假手术组（Sham组）、缺血再灌注组（I/R组）、普伐他汀预处理组（I/R+P组）、I/R+miR-93 -模拟物、I/R+P+miR-93-模拟物、I/R+Nrf2 siRNA 和 I/R+P+Nrf2 siRNA 组。检测各组心肌功能。
结果：心肌I/R损伤可导致心肌酶活性异常、炎症反应和氧化应激。但普伐他汀可显着抑制心肌酶活性，减轻炎症反应，抑制氧化应激反应，从而起到保护作用。此外，细胞实验表明，普伐他汀可减轻I/R引起的H9C2心肌细胞损伤，抑制心肌细胞凋亡，并导致促凋亡基因Bax、caspase-3和caspase-9转录水平显着降低。 ，抗凋亡基因Bcl-2明显增加，细胞活性增加。I/R诱导损伤后，miR-93水平显着上调，Nrf2水平下调。过表达miR-93或抑制Nrf2表达会导致I/R心肌损伤进一步加重，细胞凋亡率增加，心肌细胞活性降低。普伐他汀给药可抑制 miR-93，激活和促进心肌组织中的 Nrf2，并促进下游调节基因 HO-1 和 NQO1 的蛋白表达。在 I/R 模型中，给予普伐他汀。过表达 miR-93 或沉默 Nrf2 可以逆转普伐他汀对 I/R 的治疗作用。
结论：普伐他汀通过调节miR-93/Nrf2/ARE信号通路发挥心肌缺血再灌注损伤的保护作用。
关键词：普伐他汀，miR-93/Nrf2/ARE，心肌缺血再灌注损伤，保护作用
更新日期：2020-09-22
Patients and Methods: Altogether 70 male rats were selected and grouped into Sham operation group (Sham group), ischemia reperfusion group (I/R group), pravastatin pretreatment group (I/R+P group), I/R+miR-93-mimics, I/R+P+miR-93-mimics, I/R+Nrf2 siRNA, and I/R+P+Nrf2 siRNA group. The myocardial function of each group was detected.
Results: Myocardial I/R injury could lead to abnormal myocardial enzyme activity, inflammatory reaction and oxidative stress. However, pravastatin could significantly inhibit the activity of myocardial enzymes, alleviate inflammatory reaction and inhibit oxidative stress reaction, thus playing a protective role. Furthermore, cell experiments showed that pravastatin can alleviate the injury of H9C2 myocardial cells caused by I/R, inhibit the apoptosis of myocardial cells, and lead to a significant reduction in pro-apoptotic genes Bax, caspase-3 and caspase-9 transcription levels, an obvious increase in anti-apoptotic gene Bcl-2, and an increase in cell activity. After I/R induced injury, miR-93 level was significantly up-regulated and Nrf2 level was down-regulated. Over-expression of miR-93 or inhibition of Nrf2 expression would lead to further aggravation of I/R myocardial injury, increase the apoptosis rate of cells and decrease the activity of myocardial cells. Pravastatin administration could inhibit miR-93, activate and promote Nrf2 in myocardial tissue, and promote protein expression of downstream regulatory genes HO-1 and NQO1. In the I/R model, pravastatin was given. Over-expression of miR-93 or silencing Nrf2 could reverse the therapeutic effect of pravastatin on I/R.
Conclusion: Pravastatin acts as a protector on myocardial ischemia reperfusion injury by regulating miR-93/Nrf2/ARE signaling pathway.
Keywords: pravastatin, miR-93/Nrf2/ARE, myocardial ischemia reperfusion injury, protective effect
中文翻译：
普伐他汀通过调控miR-93/Nrf2/ARE信号通路对心肌缺血再灌注损伤的保护作用
目的：本研究旨在研究普伐他汀在心肌缺血再灌注（I/R）损伤中的作用机制。
患者与方法：共选取雄性大鼠70只，分为假手术组（Sham组）、缺血再灌注组（I/R组）、普伐他汀预处理组（I/R+P组）、I/R+miR-93 -模拟物、I/R+P+miR-93-模拟物、I/R+Nrf2 siRNA 和 I/R+P+Nrf2 siRNA 组。检测各组心肌功能。
结果：心肌I/R损伤可导致心肌酶活性异常、炎症反应和氧化应激。但普伐他汀可显着抑制心肌酶活性，减轻炎症反应，抑制氧化应激反应，从而起到保护作用。此外，细胞实验表明，普伐他汀可减轻I/R引起的H9C2心肌细胞损伤，抑制心肌细胞凋亡，并导致促凋亡基因Bax、caspase-3和caspase-9转录水平显着降低。 ，抗凋亡基因Bcl-2明显增加，细胞活性增加。I/R诱导损伤后，miR-93水平显着上调，Nrf2水平下调。过表达miR-93或抑制Nrf2表达会导致I/R心肌损伤进一步加重，细胞凋亡率增加，心肌细胞活性降低。普伐他汀给药可抑制 miR-93，激活和促进心肌组织中的 Nrf2，并促进下游调节基因 HO-1 和 NQO1 的蛋白表达。在 I/R 模型中，给予普伐他汀。过表达 miR-93 或沉默 Nrf2 可以逆转普伐他汀对 I/R 的治疗作用。
结论：普伐他汀通过调节miR-93/Nrf2/ARE信号通路发挥心肌缺血再灌注损伤的保护作用。
关键词：普伐他汀，miR-93/Nrf2/ARE，心肌缺血再灌注损伤，保护作用
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