杜鹃花总黄酮预处理对大鼠离体心脏缺血再灌注损伤的保护作用

Protective effect of total flavones of rhododendra pharmacological preconditioning on rat myocardial ischemic and reperfusion injury

目的观察杜鹃花总黄酮（TFR）预处理对大鼠心肌缺血再灌注损伤的保护作用及其机制。方法建立Langendorff离体大鼠心脏模型。观察心脏冠脉流量（CF）、心肌中肌酸激酶（CK）、乳酸脱氢酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）、一氧化氮合酶（NOS）及一氧化氮（NO）等的变化。用离体器官法测定家兔主动脉环张力的变化。结果12．5、25、50和100mg／L TFR—PP可明显地抑制缺血再灌致大鼠心脏CF的减少和心肌中MDA含量的升高及NO含量和NOS活性的下降；25、50和100mg／L，TFR-PP可明显地抑制心肌中CK和SOD活性的下降；50和100mg／L TFR—PP可明显地抑制心肌中LDH活性的下降。在0．033—2．70g／L范围内，TFR可分别松弛由KCl和苯肾上腺素诱导的家兔主动脉环的收缩，TFR的血管松弛作用可被内向整流型钾通道（K IR）的阻断剂BaCl2（10^-4mol／L）及大电导Ca^2＋-敏感性钾通道（BK Ca）的阻断剂TEA（3×10^-3mol／L）明显地减弱，但去除血管内皮和用前列腺环素（PGI2）合成酶抑制剂Indo（0．1mmol／L）及NO合酶抑制剂L-NAME（0．1mmol／L）预处理后对TFR的血管松弛作用无明显的影响。结论，TFR—PP对大鼠离体心脏缺血再灌注损伤有明显保护作用，其作用可能与减少自由基过氧化、增加NO生成、血管松弛及开放K IR及BK Ca等有关。

Objective To study the protective effect of total flavones of Rhododendra pharmacological preconditioning （TFR-PP） on myocardial ischemia and reperfusion injury and its mechanism in rat. Methods The isolated perfused rat heart set up by Langendorff system. Then the methylenedioxy amphetamine （MDA）and nitric oxide （ NO）, the activities of superoxide dismutase （ SOD）, lactate dehydrogenase （ LDH）, creatine phosphokinase （CK） and nitric oxide synthase （NOS） in myocardium were measured. Rabbit aorta rings were studied in organ baths, the change of rings tension was measured by a force transducer built in multi myograph system. Results 12. 5, 25,50,100 mg/L TFR-PP markedly inhibited the reduction of coronary flow, the increase of MDA content and the reduction of NO content and NOS activity in myoeardium induced by myocardial ischemia and reperfusion in isolated rat heart. 25, 50,100 mg/L TFR-PP significantly inhibited the reductions of CK and SOD activities in myocardium. 50,100 mg/L TFR-PP significantly inhibited the reduction of LDH. In the range of 0. 033,2. 7 g/L, TFR induced concentration-dependent relaxations of KCl-and phenylephrine-preconstricted endothelium-intact aorta rings, TFR-induced relaxation was significantly attenuated by pretreatment of 10^-4 mol/L BaCl2, a blocker of inward rectifier K^＋ channel （K IR） and tetraethylammonium chloride （TEA, 3 × 10^-3 mol/L）, a blocker of high conductance Ca^2＋ -sensitive K ~ channel（ BK Ca）, but it was not affected by removal of endothelium, Indo and L-NAME. Cone/us/an TFR-PP has a marked protective effect on ischemia and reperfusion injury in isolated rat heart via attenuating oxygen free radicals, increasing NO production, vasorelaxation as well as the opening of K IR and BK Ca.