IGF-1后处理与缺血后处理抑制缺血再灌注心肌损伤的对比研究

发布时间：2018-10-09 12:13

【摘要】：目的 1.将IGF-1后处理与单纯缺血再灌注相比较，明确IGF-1对缺血再灌注心肌是否具有后处理保护作用。 2.通过与缺血后处理相比较，明确IGF-1后处理对缺血再灌注心肌保护作用的程度及效应如何。 3.对比探讨IGF-1后处理及缺血后处理两者减少再灌注心肌凋亡的可能机制。方法 48只健康雄性SD大鼠随机平均分成4组：假手术组(Sham组)、缺血再灌注组(ischemia-reperfusion I/R组)、缺血后处理组(ischemicpostconditioning I-POST组)、IGF-1后处理组(IGF-1postconditioningIGF-1-POST组)。采用左冠状动脉前降支球囊垫扎法建立在体模型，除Sham组外其余各组心肌均经历45min的缺血，120min的再灌注。利用多导生理记录仪记录再灌注早期（再灌注后前30min）心脏电活动及再灌注120min时血流动力学情况；利用HE染色明确心肌病理损伤程度，心肌凋亡率采用TUNEL方法检测；ELISA法检测血清中TNF-α、IL-6、IL-10的含量；采用免疫蛋白印迹法及免疫组化法检测P~(ser-133)-CREB及Bcl-2蛋白的表达。结果 1.同I/R组相比，I-POST组和IGF-1-POST组血流动力学相关指标（HR、SBP、DBP、LVSP、LVEDP、±LVdp/dtmax）得到改善；室性早搏、室速、室颤等再灌注早期心律失常减少；心肌损伤程度及心肌凋亡率下降；血清中TNF-α、IL-6的含量下降，IL-10含量上升；蛋白P~(ser-133)-CREB及Bcl-2表达增加，上述各指标均有统计学差异（P0.05）。 2.I-POST组和IGF-1-POST组两者相比，I-POST可进一步使室性早搏、室速、室颤等再灌注早期心律失常减少，而IGF-1-POST可进一步减少血清中炎症相关因子TNF-α的含量,提高抗炎因子IL-10水平（P0.05）；而HR、SBP、DBP、LVSP、LVEDP、±LVdp/dtmax，心肌损伤程度及心肌凋亡率，，蛋白P~(ser-133)-CREB及Bcl-2表达等指标未见统计学差异（P0.05）。结论 1.心肌缺血后再灌注可诱发加重心肌损伤，而IGF-1对其具有后处理保护作用。 2.IGF-1后处理对缺血再灌注心肌保护作用的程度及效应可能与缺血后处理相当。 3.使蛋白P~(ser-133)-CREB及Bcl-2高表达，可能是IGF-1后处理和缺血后处理两者抑制心肌凋亡的共有机制。
[Abstract]:Objective 1. Comparing IGF-1 post treatment with ischemia reperfusion alone, it was determined whether IGF-1 had postprocessing protective effect on ischemia reperfusion myocardium. 2. The degree and effect of IGF-1 post-treatment on myocardial protection after ischemia and reperfusion were determined by comparing with post-ischemic treatment. 3. To explore the possible mechanism of IGF-1 post-treatment and ischemia post-treatment to reduce myocardial apoptosis after reperfusion. Methods Forty-eight healthy male SD rats were randomly divided into 4 groups: sham operation group (Sham group), ischemia-reperfusion group (ischemia-reperfusion I / R group), ischemicpostconditioning I-POST group (ischemicpostconditioning I-POST group) and IGF-1postconditioningIGF-1-POST group. In vivo model was established by balloon ligation of anterior descending branch of left coronary artery. The myocardium of all groups except Sham group underwent 45min ischemia and reperfusion for 120 minutes. The electrocardiogram of early reperfusion (30min before and after reperfusion) and hemodynamics during reperfusion 120min were recorded by multichannel physiological recorder, the degree of myocardial injury was determined by HE staining, and the myocardial apoptosis rate was detected by TUNEL method. The expression of TNF- 伪 -CREB and Bcl-2 protein in serum was detected by ELISA method, and the expression of P- (ser-133) -CREB and Bcl-2 protein was detected by immunoblotting and immunohistochemistry. Result 1. Compared with I / R group, HR,SBP,DBP,LVSP,LVEDP, 卤LVdp/dtmax in I-POST group and IGF-1-POST group were improved, ventricular premature beat, ventricular tachycardia, ventricular fibrillation and other early reperfusion arrhythmias, myocardial injury degree and myocardial apoptosis rate were decreased. The content of TNF- 伪 -IL-6 decreased and the content of IL-10 increased, the expression of protein P- (ser-133) -CREB and Bcl-2 increased, and the above indexes were significantly different (P0.05). Compared with IGF-1-POST group and 2.I-POST group, I-POST could further reduce ventricular premature beat, ventricular tachycardia, ventricular fibrillation and other early reperfusion arrhythmias, while IGF-1-POST could further reduce the content of TNF- 伪 in serum and increase the level of anti-inflammatory factor IL-10 (P0.05). However, there was no significant difference in myocardial injury degree, myocardial apoptosis rate, protein P- (ser-133) -CREB and Bcl-2 expression in HR,SBP,DBP,LVSP,LVEDP, 卤LVdp/dtmax, (P0.05). Conclusion 1. Myocardial ischemia reperfusion can induce and aggravate myocardial injury, but IGF-1 can protect it from post-treatment. The degree and effect of 2.IGF-1 post-treatment on myocardial protection of ischemia-reperfusion may be similar to that of post-ischemic treatment. 3. The overexpression of P- (ser-133) -CREB and Bcl-2 may be the common mechanism of inhibiting myocardial apoptosis by both post-treatment of IGF-1 and post-treatment of ischemia.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R363

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