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目的:研究线粒体通透性转换(PT)孔在精脒介导的心肌缺血/再灌注损伤中的作用。方法:采用Langendorff灌流离体大鼠心脏,全心停灌30min,复灌120min造成心肌缺血复灌模型。采用高效液相色谱法测定心肌组织精脒含量;复灌前10min给予不同浓度精脒,记录左室收缩压(LVSP)、左室压上升/下降最大速率(±dp/dtmax)和左室舒张末期压力(LVEDP);用紫外分光光度法检测复灌10min的冠状动脉(冠脉)流出液乳酸脱氢酶(LDH)活性;用TTC染色法测心肌梗死面积。检测不同浓度精脒对心肌线粒体PT孔开放改变(520nm吸光度变化)。结果:与对照组比较,大鼠心肌缺血期及再灌期精脒含量均减少(P<0.05);与单纯缺血/复灌组相比,于复灌前10min给予线粒体通透性转换孔特异性阻断剂环孢菌素A(CsA 0.2mol/L)和精脒(0.1mol/L、1μmol/L、5μmol/L),左室收缩舒张功能改善,其中LVSP上升(P<0.01),LVEDP下降(P<0.01),±dp/dtmax提高(P<0.01);冠脉流出液中LDH含量明显减少(P<0.01),梗死面积减少(P<0.01)。而于复灌前10min给予精脒(10μmol/L,15μmol/L),与单纯缺血/复灌组比较,LVSP均明显下降(均P<0.01),LVEDP明显上升(P<0.01),±dp/dtmax下降(P<0.01);复灌10min后冠脉流出液中LDH含量明显增加(P<0.01),梗死面积均增加(均P<0.01);在分离的线粒体给予精脒,高浓度PT孔开放幅度增加;低浓度开放受到抑制。结论:精脒可通过抑制或增强线粒体PT孔开放而对缺血/再灌心肌产生保护或加重损伤的作用。
AIM: To investigate the role of mitochondrial permeability transition (PT) pores in spermidine-mediated myocardial ischemia / reperfusion injury. Methods: The heart of isolated rat was perfused with Langendorff. The rats were perfused with 30 min of heart infusion and reperfused for 120 min to induce myocardial ischemia and reperfusion. The contents of spermine in myocardial tissue were determined by high performance liquid chromatography (HPLC). The concentrations of spermine in different concentrations were given 10 min before reperfusion. The left ventricular systolic pressure (LVSP), maximum ± dp / dtmax and left ventricular diastolic End-stage pressure (LVEDP); Lactate dehydrogenase (LDH) activity of coronary artery (coronary) efflux was detected by UV spectrophotometry 10min after reperfusion; myocardial infarction size was measured by TTC staining. Detection of different concentrations of spermine on myocardial mitochondrial PT pore opening changes (520nm absorbance changes). Results: Compared with the control group, the contents of spermine in myocardial ischemia and reperfusion were decreased (P <0.05). Compared with the ischemia / reperfusion group, mitochondrial permeability transition Pore-specific blockers Cyclosporine A (CsA 0.2mol / L) and spermidine (0.1mol / L, 1μmol / L, 5μmol / L) improved left ventricular systolic and diastolic function, (P <0.01), ± dp / dtmax increased (P <0.01). The content of LDH in coronary effluent decreased significantly (P <0.01) and infarct size decreased (P <0.01). (10μmol / L, 15μmol / L) 10min before reperfusion, LVSP decreased significantly (all P <0.01), LVEDP increased significantly (P <0.01) dp / dtmax decreased (P <0.01); LDH content in coronary effluent increased significantly (P <0.01) and infarct size increased 10 min after reperfusion (all P <0.01) PT pore opening increased; low concentration of open inhibition. Conclusion: Spermidine can protect or aggravate the ischemia / reperfusion myocardium by inhibiting or enhancing the opening of mitochondrial PT.