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目的研究心肌细胞线粒体钙激活钾通道(MitoKCa)与线粒体ATP敏感钾通道(MitoKATP)在肢体远距预处理(RPC)心肌保护中的作用。方法雄性SD大鼠72只,分为9组:单纯缺血复灌(I/R)组、RPC组、MitoKATP开放剂(DZ)组、MitoKCa开放剂NS1619组、MitoKCa开放阻断剂RPC+paxilline组、MitoKATP开放阻断剂RPC+5-HD(5-hydroxydeconate)组、RPC+NS1619+5-HD组、RPC+paxilline+DZ组和RPC+paxilline+5-HD组,每组8只。RPC模型用结扎大鼠股动脉5min,松开复灌5min,共4个循环的方法制备。各组I/R模型通过结扎离体心脏冠状动脉前降支30min,松开复灌120min进行制备。检测各组心脏血流动力学变化,TTC染色法测量心肌梗死面积,可见分光光度法检测冠脉流出液中LDH含量。结果与I/R组相比,NS1619(10μmol/L)和DZ(50μmol/L)作用与远距预处理RPC组相似,改善复灌后心功能,减小心肌梗死面积,抑制了LDH释放(P<0.01),但与RPC组相比差异无统计学意义(P>0.05)。给予Paxilline(1μmol/L)或5-HD(100μmol/L),取消了RPC的心肌保护作用(P<0.01)。阻断MitoKCa和MitoKATP中的一种通道,开放另一种通道仍可起到心肌保护作用,且与RPC组无明显差异(P>0.05);同时给予两种通道的阻断剂,发现与单独阻断一种通道相比,心肌细胞损伤程度加大(P<0.01)。结论心肌细胞线粒体钙激活钾通道MitoKCa和线粒体ATP敏感钾通道MitoKATP开放都参与了RPC的心肌保护作用,两者发挥作用的方式可能是相互独立的,但作用结果具有协同性。
Objective To investigate the role of mitochondrial calcium-activated potassium channel (MitoKCa) and mitochondrial ATP-sensitive potassium channel (MitoKATP) in myocardial remodeling (RPC) myocardial protection. Methods 72 male Sprague-Dawley rats were divided into 9 groups: I / R group, RPC group, MitoKATP opener (DZ) group, MitoKCa opener NS1619 group, MitoKCa open blocker RPC + paxilline Group, MitoKATP open-label RPC + 5-HD group, RPC + NS1619 + 5-HD group, RPC + paxilline + DZ group and RPC + paxilline + 5-HD group. The RPC model was prepared by ligation of rat femoral artery for 5 min, reperfusion for 5 min, and 4 cycles. The I / R model of each group was prepared by ligating the anterior descending branch of isolated coronary artery for 30 minutes and releasing the reperfusion for 120 minutes. Cardiac hemodynamic changes were detected in each group. TTC staining was used to measure the area of myocardial infarction. The content of LDH in coronary effusion was measured by spectrophotometry. Results Compared with I / R group, the effect of NS1619 (10μmol / L) and DZ (50μmol / L) was similar to that of the remote pretreatment RPC group, which improved the cardiac function after reperfusion, reduced the area of myocardial infarction and inhibited the release of LDH P <0.01), but there was no significant difference compared with RPC group (P> 0.05). Administration of Paxilline (1 μmol / L) or 5-HD (100 μmol / L) abolished the cardioprotective effects of RPC (P <0.01). Blocking MitoKCa and MitoKATP in one of the channels, open another channel can still play a cardioprotective role, and no significant difference with the RPC group (P> 0.05); also given two kinds of channel blockers found to be alone Compared with blocking a channel, myocardial injury increased (P <0.01). Conclusions Myocardial mitochondrial calcium-activated potassium channel MitoKCa and mitochondrial ATP-sensitive potassium channel MitoKATP open circuit are involved in the myocardial protection of RPC. The two modes of action may be independent, but the results are synergistic.