外源性H2S恢复老龄大鼠心肌缺血后适应对I/R损伤的缓解作用

基础医学与临床 ›› 2016, Vol. 36 ›› Issue (9): 1199-1205.

外源性H2S恢复老龄大鼠心肌缺血后适应对I/R损伤的缓解作用

李丽娜¹,孙伟铭¹,高君²,王跃虹¹,魏璨¹,徐长庆¹,李鸿珠¹

1. 哈尔滨医科大学
2. 哈尔滨市第一医院

收稿日期:2015-10-19 修回日期:2015-12-29 出版日期:2016-09-05 发布日期:2016-08-30
通讯作者: 李鸿珠 E-mail:hongzhuli61@163.com
基金资助:
国家自然科学基金;国家自然科学基金;国家自然科学基金;黑龙江省自然科学基金

Exogenous H2S restores ischemic postconditioning-induced protection against I/R injury in heart of aging rats

Received:2015-10-19 Revised:2015-12-29 Online:2016-09-05 Published:2016-08-30
Contact: Hong-Zhu LI E-mail:hongzhuli61@163.com

摘要/Abstract

摘要： 目的探讨外源性硫化氢（H2S）恢复缺血后适应（PC）对老龄大鼠心肌的保护作用及相关机制。方法将青年和老龄大鼠随机分别分为对照组、缺血/再灌注（I/R）组和PC组，老龄大鼠另加NaHS干预组。用Langendorff离体灌流装置，复制大鼠心肌I/R损伤和PC模型。比色法测定冠脉流出液LDH、CK活性和心肌组织匀浆SOD活性、MDA含量及H2S产率；透射电镜检测心肌超微结构；TTC染色测定心肌梗死面积；TUNEL染色检测心肌细胞凋亡；Western blot检测caspase-3、caspase-9、Bcl-2及胱硫醚-γ-裂解酶（CSE）的表达。结果无论青年还是老龄大鼠，与对照组比较，I/R降低H2S产率、SOD活性和CSE表达，增加LDH和CK活性、MDA含量、心肌损伤、细胞凋亡、心肌梗死面积、caspase-3、caspase-9及Bcl-2的表达（P<0.01）；与I∕R组比较，青年大鼠的PC减轻I/R损伤及细胞凋亡（P<0.01），而老龄大鼠的PC丧失了对心肌的保护作用；外源性H2S 恢复了老龄大鼠的PC对I/R损伤的保护作用。结论外源性H2S能够恢复老龄大鼠PC对心肌的保护作用，其机制与抗氧化、清除自由基、抑制细胞凋亡有关。

关键词: 硫化氢, 缺血-再灌注损伤, 缺血后适应, 细胞凋亡, 老龄大鼠

Abstract: Objective To explore the myocardial protective effects and possible mechanisms of hydrogen sulfide (H2S) on the recovery of ischemic post-conditioning (PC) in the aging rats. Methods Wistar young and aging rats were randomly divided into control group, ischemia/reperfusion (I/R) group, ischemic post-conditioning (PC) group. In addition, aging rats were treated with NaHS (PC+NaHS). The model of myocardial I/R injury and PC in isolated rats hearts was induced with Langendorff system; LDH, CK activities of coronary effluent and SOD activity and MDA content as well as H2S production rate of myocardial tissue homogenate were measured by colorimetric method; Myocardial ultrastructure was detected by transmission electron microscope; The myocardial infarct size was measured by TTC staining; Myocardial cell apoptosis was detected by TUNEL staining; The expression of Bcl-2, caspase-3 and caspase-9 was detected by Western blot. Results Compared with the control group, I/R decreased H2S production rate, SOD activity and CSE expression, increased LDH and CK activity, MDA content, myocardial injury, apoptosis, myocardial infarct size, caspase-3 and caspase-9 and Bcl-2 expression(P<0.01); Compared with the I/R group, PC reduced I/R injury and apoptosis in the young hearts (P<0.01), however, PC lost myocardial protective effect in the aging hearts; Exogenous H2S restored the PC-induced cardioprotection in aging hearts. Conclusion Our results suggest that exogenous H2S restores the myocardial protective effect of PC via anti-oxidation, scavenging free radical and inhibiting apoptosis.

Key words: hydrogen sulfide, ischemia/reperfusion injury, ischemic post-conditoning, apoptosis, aging rats

中图分类号:

R542.2

李丽娜孙伟铭高君王跃虹魏璨徐长庆李鸿珠. 外源性H2S恢复老龄大鼠心肌缺血后适应对I/R损伤的缓解作用[J]. 基础医学与临床, 2016, 36(9): 1199-1205.

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