缺血后处理对缺血／再灌注大鼠心肌间质保护效应机制的探讨

目的：观察缺血后处理（IPIC）对缺血／再灌注（I／R）大鼠心肌基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶抑制剂-2（TIMP-2）变化的影响，探讨IPTC保护I／R心脏间质的机制。方法：24只健康雄性SD大鼠随机分为3组（n：8）：假手术组（SC组）、I／R组和IPTC组。记录各组左室血流动力学变化，观察心肌胶原含量，测定血浆中肌酸激酶（CK）和乳酸脱氢酶（LDH）浓度。以Westernblot法测定心肌组织中MMP-2和TIMP-2蛋白表达水平，以实时定量PCR（RT-PCR）法检测MMP-2和TIMP-2的表达水平。结果：与sC组相比，I／R组心肌胶原含量和左室舒缩功能明显降低，血浆cK、LDH活力和心肌MMP-2蛋白表达及mRNA水平明显升高，TIMP-2蛋白及mRNA水平明显降低；而IPTC组，大鼠心肌胶原含量和左室舒缩功能明显升高，血浆cK、LDH活力和心肌MMP-2蛋白表达及mRNA水平降低，TIMP-2蛋白及mRNA水平升高。结论：IPTC对再灌注损伤心肌间质有保护作用，其机制可能与抑制心肌中MMP-2表达，促进TIMP-2表达有关。

The cardioprotective effects of ischemic postconditioning on myocardial interstitium following ischemic/reperfusion in rats

Objective： To investigate the effects of ischemie posteonditioning （I FIE） on the changes of matrix metalloproteinases-2 （MMP-2） and tissue inhibitor of metalloproteinase-2 （TIMP-2） protein and mRNA levels in rat heart subjected to ischemia/repeffusion, and explore the mechanism by which IPTC protects myocardial interstitium following ischemic/reperfusion （I/R）. Methods： Twenty four healthy male SD rats were randomly divided into 3 groups （ n = 8） ： sham control （SC） group, I/R group and IPTC group. The parameters of left ven- tricular function including left ventricular systolic pressure （LVSP） and its derivate （± dp/dt ） were measured; the amount of myocardial colla- gen contents was determined by hydroxyproline quantification; the plasma activity of creatine kinase （CK） and lactate dehydrogenase （LDH） was detected; the protien levels of MMP-2 and TIMP-2 was measured by Western blot and the mRNA levels of MMP-2 and TIMP-2 was detect- ed by real-time PCR. Results： The myocardial collagen contents, left ventricular function and the protein and mRNA levels of TIMP-2 were significantly decreased in I/R group compared with those of SC group, wherease the activities of CK and LDH in the plasma and the protein and mRNA levels of MMP-2 were significantly enhanced in I/R group when compared to SC group. Compared with I/R group, the myocardial collagen contents, left ventricular function and the protein and mRNA levels of TIMP-2 were increased in IFFC group, the activities of CK and LDH in the plasma and the protein and mRNA level of MMP-2 were decreased in IPTC group. Conchusion： These findings indicate that WI＇C has protective effects on myocardial interstitial after the myocardial ischemia/reperfusion injury, and IPTC may exert its cardioprotectve effect via inhibiting MMP-2 and enhancing TIMP-2 expression in cardiac muscle.