银杏达莫注射液抑制大鼠离体心脏缺血/再灌注损伤的机制研究

Inhibitory effect of ginkgo-dipyridamole injection on ischemia/reperfusion injury in rat hearts in vitro

目的:观察银杏达莫注射液预处理对大鼠离体心脏缺血/再灌注损伤的影响,并探讨其可能的作用机制。方法:SD雄性大鼠40只随机分成5组(n=8):正常对照(NC)组、缺血/再灌注(I/R)组、缺血预处理(IPC+I/R)组、银杏达莫注射液预处理(GD+I/R)组和银杏达莫+氯化镧预处理(GD+LaCl3+I/R)组。观察各组相同时点(预灌30 min稳定点,缺血30 min,再灌5 min、30 min、60 min)的心功能指标,包括心率(HR)、左室收缩压(LVSP)和室内压变化速率(±dp/dt max),同时收集各时点冠脉流出液,检测其中乳酸脱氢酶(LDH)和肌酸激酶(CK)活性。实验结束后检测心肌线粒体Ca2+浓度和α-酮戊二酸脱氢酶(α-OGDH)含量。结果:与I/R组比较,IPC+I/R组和GD+I/R组在心脏再灌注期各项心功能指标均得到改善(P<0.05);心肌LDH和CK的释放量降低(P<0.01);线粒体内Ca2+超载降低(P<0.01),且线粒体内α-OGDH含量升高(P<0.05);而GD+I/R组中银杏达莫对心肌的保护作用被LaCl3抑制(P<0.05)。结论:银杏达莫可能通过抑制钙超载、增强线粒体酶活性以稳定线粒体能量代谢,从而缓解缺血/再灌注诱导的心肌细胞损伤。

AIM：To investigate the effect of ginkgo-dipyridamole injection （GD） on ischemia/reperfusion （I/R） injury in rat hearts in vitro and its possible mechanism. METHODS：Forty male Sprague-Dawley rats were randomly divided into 5 groups （n=8）： normal control （NC） group, I/R group, ischemic preconditioning （IPC）＋I/R group, GD＋I/R group and GD＋LaCl3＋I/R group. Cardiac function indexes, including heart rate （HR）, left ventricular systolic pressure （LVSP） and the maximal rise/fall rate of left ventricular pressure （±dp/dtmax）, were detected at 5 time points, including stabilizing point, 30 min after ischemia, and 5, 30 and 60 min after reperfusion. The activity of lactate dehydrogenase （LDH） and creatine kinase （CK） in coronary effluent at the five time points was assayed. The concentration of Ca2＋ and the content of α-ketoglutarate dehydrogenase （α-OGDH） in myocardial mitochondria were determined at the end of the whole experiment. RESULTS：Compared with I/R group, the cardiac function indexes in IPC＋I/R and GD＋I/R groups were improved at the reperfusion period （P〈0.05）, the activity of LDH and CK in coronary effluent and the concentration of Ca2＋ in mitochondria were significant reduced （P〈0.01）, and the content of α-OGDH was increased （P〈0.05）. However, the protective effect of GD was inhibited by LaCl3 （P〈0.05）. CONCLUSION：GD protects rat hearts against I/R injury by inhibiting calcium overload and improving mitochondrial enzyme activity to stabilize mitochondrial energy metabolism.