异甜菊醇抗豚鼠离体心脏缺氧复灌损伤作用

目的　拟证实双萜类化合物异甜菊醇抗豚鼠离体心脏缺氧复灌损伤作用及与线粒体ATP敏感性钾通道 (mito KATP)的关系。方法　Langendorff装置逆向心脏灌注。预先灌注异甜菊醇 1,5和 10μmol·L- 1,5min ,流速约为 9.5mL·min- 1,全心停灌 30min ,复灌 2 0min ,观察心脏舒缩功能、冠脉流出液酶学和心肌组织学改变。结果异甜菊醇预处理有效减轻缺氧复灌引起的左室舒缩功能下降 ,降低冠脉流出液中乳酸脱氢酶和肌酸激酶浓度 ;延迟停灌后心脏出现挛缩的时间。mito KATP关闭剂 5 羟基癸酸 10 0 μmol·L- 1可部分逆转异甜菊醇 10 μmol·L- 1的心肌保护作用。光学和电子显微镜观察结果表明 ,异甜菊醇预处理可减轻缺氧复灌引起的心肌纤维和线粒体损伤。结论　异甜菊醇 1～ 10 μmol·L- 1预灌注可有效减轻豚鼠离体心肌缺氧复灌引起的损伤 ,该作用可能与mito KATP的开放有关。

Effects of isosteviol against myocardium injury induced by global ischemia-reperfusion in isolated guinea pig hearts

AIM To demonstrate the cardioprotective effect of isosteviol against myocardium injury induced by ischemia-reperfusion and possible interaction with mitochondria ATP-sensitive K⁺ channel (mito-K_ATP) in vitro. METHODS The isolated guinea-pig hearts were Langendorff-perfused with modified Tyrode buffer solution. Isosteviol 1, 5 and 10 μmol•L^-1 was preinfused for 5 min with the velocity of 9.5 mL•min^-1, respectively, followed by ischemia 30 min/reperfusion 20 min (n=8 in each group). The cardiac functions, coronary arterial flow, and lactate dehydrogenase (LDH) and creatine kinase(CK) activities in the flow were measured prior to ischemia and at the end of reperfusion respectively. The pathological changes and ultrastructure of myocardium were observed by light- and electron-microscope. RESULTS The cardiac functions and structure were deteriorated by global ischemia-reperfusion. The injury of left ventricular systolic-diastolic function and increase in LDH and CK activities in coronary flow induced by ischemia-reperfusion could be weaken effectively by pretreatment with isosteviol and ischemia preconditioning (IPC). The time of cardiac contracture was delayed by isosteviol and IPC. The cardioprotective effect of isosteviol 10 μmol•L^-1 could be antagonized partly by pretreatment of a mito-K_ATP closurer, 5-hydroxydecanoic acid 100 μmol•L^-1. The histopathological changes in mitochondria and myocardium destroyed by ischemia/reperfusion were alleviated markedly by isosteviol. CONCLUSION The cardioprotective effect by isosteviol against ischemia-reperfusion is demonstrated in Langendorff perfused guinea pig heart in vitro, which may be mediated by mito-K_ATP.