ATP敏感性钾通道开放剂Cromakalim心脏保护机制的初步探讨

The Possible Mechanisms of Cardioprotective Effects of KATP Channel Opener Cromakalim

本工作用大鼠离体灌流心脏血再灌注损伤模型观察了K_(ATP)通道开放剂克罗卡林(Cromakalim,CRK)的心脏保护作用。结果表明,CRK能明显减少缺血再灌注损伤心肌的LDH及蛋白的漏出(P<0.01),降低脂质过氧化产物MDA的含量(P<0.01),心肌组织及心肌线粒体钙含量也显著降低(P<0.01)。CRK明显抑制心肌线粒体的最大^(45)Ca^(2+)摄取量及摄钙速率。CRK的上述作用均能被K_(ATP)通道阻断剂格列苯脲(Glybenclamide,GLB)所消除。上述结果表明,CRK能通过开放K_(ATP)通道发挥心脏保护作用,其心脏保护作用的机制可能与膜稳定作用、抑制氧自由基的产生及抑制心肌细胞和心肌线粒体钙超载有关。

On the model of ischaemia/reperfusion model of isolated rat heart, we studied the protective effects of Cro-makalim (CRK). The results shown that CRK decreased the leakage of intracellular LDH as well as proteins significantly (P <0. 01), the content of MDA in reperfusate and eardiomyocytes was reduced (P <0. 01), furthermore, the calcium content of cardiomyocytes and cardiomyocytes was reduced in CRK treated group remarkably ( P < 0. 01), The speed and maximum 45Ca2 +uptake of mitochondria (mito) were inhibited sygnificantly {P < 0. 01). The above effects of CRK were abolished by specific KATP channel blocker glybenclamide (GLB) . These results revealed that CRK is possessed of eardioprotection by opening KATP channel. These protective effects may result from sbabilizing cell membrane, inhibiting the production of free radical as well as inhibiting calcium overload of cardiomyocytes and mitochondria.