依布硒啉通过调节MAPK通路发挥心肌缺血再灌注保护作用的研究

吴华军; 翟昌林; 黄明德; 沈伟锋; 邹洪兴; 邵平扬; 楼永良

doi:10.16766/j.cnki.issn.1674-4152.000148

依布硒啉通过调节MAPK通路发挥心肌缺血再灌注保护作用的研究

doi: 10.16766/j.cnki.issn.1674-4152.000148

1. 温州医科大学检验医学院生命科学学院, 浙江温州 325000;
2. 嘉兴市第一医院检验科, 浙江嘉兴 314000;
3. 嘉兴市第一医院心内科

基金项目:

浙江省中医药科技计划项目(2015ZA203)；浙江省医药卫生计划项目(2015KYB387)

详细信息

通讯作者:
楼永良,E-mail:louyongliang2013@163.com

中图分类号: R542.22;R364.12
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出版历程
- 收稿日期: 2017-02-10
- 网络出版日期: 2022-07-22

Protective effect of Ebselen on myocardial ischemia reperfusion injury through regulating MAPK pathway

School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China

摘要

摘要: 目的研究依布硒啉对心肌缺血再灌注的保护作用及与MAPK通路的相关性。方法将36只雄性Wistar大鼠随机分为4组,分别为假手术组(Sham)、缺血再灌注对照组(IR-Control)、依布硒啉+缺血再灌注组(Ebselen+IR)和依布硒啉组(Ebselen)。建立心肌缺血再灌注模型。通过HE染色观察及组织学损伤评分评价各组心肌凋亡坏死情况,Elisa法测定血清TNF-α、IL-6、组织TGFβ1表达情况,蛋白免疫印迹法测定各组MAPK通路相关蛋白表达情况。结果相较于缺血再灌注对照组,依布硒啉预处理后显著降低了再灌注所导致的心肌坏死、炎症和水肿,在组织学损伤评分上分值更低,依布硒啉预处理显著降低了缺血再灌注所造成的TNF-α上升(P<0.05)及IL-6、TGFβ1的上升(均P<0.01)。缺血再灌注损伤组的JNK和p38的磷酸化水平较假手术组显著增加,p-JNK上升了0.34±0.06,p-p38上升了0.42±0.10,p-ERK1/2下降了0.35±0.07,均P<0.001。缺血再灌注+依布硒啉组则减轻了由缺血再灌注所造成的磷酸化JNK和p38的上升与ERK1/2水平的降低,p-JNK下降了0.17±0.05(P<0.001),p-p38下降了0.16±0.03(P<0.01),p-ERK1/2提高了0.09±0.02(P<0.05)。结论依布硒啉处理可有效发挥心肌缺血再灌注保护作用,其具体机制可能与MAPK通路调节相关。
- 依布硒啉 /
- MAPK通路 /
- 心肌缺血再灌注
Abstract: Objective To research the correlation between the protective effect of Ebselen on myocardial ischemia reperfusion injury and MAPK pathway. Methods Thirty-six male Wistar rats were randomly divided into sham operation group(Sham), Ischemia reperfusion group (IR-Control), Ebselen + ischemia reperfusion group (Ebselen+IR) and Ebselen group (Ebselen). The myocardial ischemia reperfusion rat model was established. The myocardial apoptosis and necrosis were evaluated by injury score and observed by HE staining; The expression of serum TNF-α, IL-6, and tissue TGFβ1 were detected by ELISA, and the expression of MAPK pathway related proteins were detected by Western blotting. Results Compared with ischemia reperfusion group, Ebselen pretreatment significantly decreased myocardial necrosis, inflammation and edema, histological injury score, Ebselen pretreatment significantly reduced TNF-α induced by ischemia reperfusion (P<0.05) and also IL-6, TGFβ1 (P<0.01). Besides, ischemia reperfusion + Ebselen group reduced the level of ERK1/2 and reduced the expression of phosphorylation of JNK and p38 induced by ischemia reperfusion injury, p-JNK increased by 0.34±0.06, p-p38 increased by 0.42±0.10, p-ERK1/2 decreased by 0.35±0.07, P<0.001. Ebselen + ischemia reperfusion group increased the level of ERK1/2 and reduce the phosphorylation of JNK and p38 caused by ischemia reperfusion injury, p-JNK decreased by 0.17±0.05 (P<0.001), p-p38 decreased by 0.16±0.03 (P<0.01), p-ERK1/2 increased 0.09±0.02 (P<0.05). Conclusion Ebselen treatment played a protective effect on myocardial ischemia reperfusion injury and its mechanism may be related to the MAPK pathway.
- Ebselen /
- MAPK pathway /
- Myocardial ischemia reperfusion injury