缺血后处理对缺血再灌注大鼠心肌MMP-2表达及NO含量的影响

Effect of Ischemic Postconditioning on Expression of Myocardical MMP-2and Nitric Oxide Level in Ischemia-reperfusion Rats

目的:观察缺血后处理对缺血再灌注损伤大鼠心肌MMP-2及一氧化氮的影响,探讨缺血后处理保护心肌间质的分子机制。方法:24只SD大鼠随机分为3组,假手术组(SC组)、缺血再灌注组(I/R组)和缺血后处理组(IPTC组)。记录各组左室血流动力学变化,观察心肌胶原含量,测定血浆一氧化氮(nitric oxide,NO)、肿瘤坏死因子-α(necrosis factor-α,TNF-α)和白细胞介素-6(intefliukine-6,IL-6)浓度改变。以RT-PCR法测定心肌基质金属蛋白酶-2(MMP-2)的表达。结果:与对照组相比,I/R组血浆TNF-α、IL-6明显升高,NO降低,心肌MMP-2表达明显增多,而心肌胶原含量降低、左室舒缩功能明显受损。IPTC组在血浆TNF-α和IL-6浓度明显降低,NO明显升高的同时,心肌MMP-2表达明显降低,而心肌胶原含量、左室舒缩功能明显高于I/R组。结论:IPTC对心肌的保护作用之一可能是通过NO增多,减少炎性介质的释放,抑制MMP-2的表达,减轻心肌间质的损伤而实现的。

Objective：To investigate the effect of ischemic postconditioning（IPTC）on expression of myocardial MMP-2and nitric oxide level in ischemia-reperfusion rats and study the molecular mechanism of IPTC on myocardial interstitium protection.Methods：24 rats were randomly divided into 3groups：sham control（SC）group,ischemic/reperfusion（I/R）group and IPTC group.The left ventricular peak systolic pressure and its derivative（±dp/dt）were calculated.Myocardial collagen amount was determined.The concentration of plasma nitric oxide（NO）,tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）were detected.The mRNA level of MMP-2 was measured by RT-PCR.Results：Compared with SC group,I/R group has significantly enhanced plasma TNF-αand IL-6level,reduced plasma NO concentration and increased myocardial MMP-2mRNA level.In addition,the concentration of myocardial collagen was reduced,and left ventricular diastolic and systolic function was significantly impaired in I/R group.However,in IPTC group,plasma TNF-αand IL-6level were reduced,and plasma NO concentration was significantly increased.At the same time,the expression of myocardial MMP-2was decreased obviously.Furthermore,the content of myocardial collagen was increased,and the left ventricular diastolic and systolic function was significantly enhanced than that of I/R group.Conclusion：Protective effect of IPTC on myocardial interstitium is possibly due to increased plasma NO concentration and reduced release of inflammatory mediators,leading to the inhibition of MMP-2 expression and reduction of myocardial interstitium injury.