收稿日期: 2018-06-22
网络出版日期: 2018-12-24
基金资助
国家自然科学基金面上资助项目(81670362);国家自然科学基金面上资助项目(81470515);嘉定区科委卫生系统科研资助项目(2014-KW-02)
Effectiveness of activation of sigma-1 receptor on reducing myocardium injury in ischemia reperfusion
Received date: 2018-06-22
Online published: 2018-12-24
[目的] 研究 sigma-1 受体的激活与抑制对心脏缺血再灌注损伤的作用. [方法] C57BL/6 小鼠经过 3 d 尾静脉注射 sigma-1 受体抑制剂 BD1047, sigma-1 受体激动剂 SA4503 或生理盐水后施行心脏缺血再灌注手术. 术后对小鼠心脏进行 TTC/Evans 蓝双染色并计算心脏梗死区 (infarction area, INF) 与危险区 (area at risk, AAR) 比值(INF/AAR), 同时对心肌组织采用蛋白免疫印迹法检测凋亡相关蛋白 Bcl-2, Bax, Caspase-3 的表达水平. [结果] 接受了 sigma-1 受体抑制剂 BD1047 预处理的小鼠, 其 INF/AAR 值远大于对照组 ($P\!<$0.05), 心肌组织中促凋亡相关蛋白的表达水平升高, 抗凋亡相关蛋白的表达水平降低. 而接受 sigma-1 受体激动剂 SA4503 预处理的小鼠, 其 INF/AAR 值远小于对照组 ($P\!<$0.05), 心肌组织中促凋亡相关蛋白的表达水平降低, 抗凋亡相关蛋白的表达水平升高. [结论] Sigma-1 受体的激活能够改善心脏缺血再灌注损伤, 而抑制 sigma-1 受体则会加重心脏缺血再灌注损伤.
廖小平, 喻溥蛟, 许嘉鸿 . Sigma-1 受体激活减轻心脏缺血再灌注损伤[J]. 上海大学学报(自然科学版), 2018 , 24(6) : 853 -860 . DOI: 10.12066/j.issn.1007-2861.2096
[Objective] This paper attempts to investigate whether sigma-1 receptor (Sig1R) activation attenuate myocardial ischemia reperfusion injury (MIRI) and whether Sig1R inhibition exacerbates MIRI in mice model. [Methods] C57BL/6 mice are injected via tail vein with BD1047 (Sig1R inhibitor), SA4503 (Sig1R activator) or saline 3 days before MIRI surgery. Then, double-staining technique and western blot analysis are performed on myocardium tissue. [Results] Mice that have received BD1047 pretreatment demonstrate a significant increase in the myocardial infarction size after I/R compared with control group ($P\!\!<$0.05), and a significantly increased expression of Bax and Caspases-3 proteins and a significantly reduced expression of Bcl-2 protein compared with sham control, MIRI control and sham BD1047 groups ($P\!<$0.05). Mice that have received SA4503 pretreatment demonstrate a significant reduction in myocardial infarction size after I/R compared with control group ($P\!<$0.05), and a significantly reduced expression of Bax and cleaved Caspases-3 proteins and a significantly increased expression of Bcl-2 protein compared with sham control, MIRI control and sham SA4503 groups ($P\!<$0.05). [Conclusions] SA4503 protects MIRI and reduces myocardial infarction whereas BD1047 deteriorates MIRI and augment myocardial infarction, and these effects may be achieved through activation or inhibition of Sig1R.
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