碘化N-正丁基氟哌啶醇减轻大鼠心肌缺血再灌注损伤作用的机制研究

目的：探讨碘化N-正丁基氟哌啶醇（F2）减轻大鼠心肌缺血再灌注损伤的分子生物学机制。方法：用大鼠在体心肌缺血再灌注模型，通过测定血清中肌酸激酶、乳酸脱氢酶的活性观察心脏损伤的情况；通过测定心肌组织中髓过氧化物酶、超氧化物歧化酶、丙二醛的变化，观察中性粒细胞浸润、氧自由基及脂质过氧化的情况。Westemblot法测定心肌缺血组织中早期生长反应基因-1（Egr-1）蛋白水平的变化。结果：与对照组比，反义核苷酸组及反义核苷酸＋F2组Egr-1蛋白表达明显减少（P〈0．05），炎症反应及心肌损伤程度明显减弱（P〈0．05）；反义核苷酸＋F2组与反义核苷酸组比。Egr-1蛋白表达无统计学意义（P〉0.05），心肌损伤及炎症反应程度明显减轻（P（0．05）。结论：F2可通过抑制Egr-1蛋白表达，起到减轻心肌缺血再灌注损伤的作用，除抑制Egr-1蛋白的高表达外，F2还可通过其他机制起到抗心肌缺血再灌注的作用。

The Protective Effect of N-n-butyl Haloperidol Iodide on Myocardial Ischemia-Reperfusion Injury in Rats

Objective:To study the mechanism of N-n-butyl haloperidol iodide(F_2)attenuating myocardial ischemia-reperfusion injury in rats.Methods:The rat experimental models in vivo were established.The system of BL-420 was used to monitor haemodynamics.The levels of creatinkinase,lactic acid dehydrogenase,myeloperoxidase,superoxide dismutase,malondialdehyde were also determined.The expression level of Egr_1 protein in myocardial tissue was exa-mined by Western blot.Results:Compared with the control group,the antisense nucleotide group,antisense nucleotide and F_2 group could inhibit the expression levels of Egr-1 protein(P<0.05),but there was no difference between the antisense nucleotide group and the antisense nucleotide and F_2 group(P>0.05),they both could protect myocardial tissue from ischemia-reperfusion injury.Conclusion:F_2 can protect myocardium from ischemia-reperfusion by inhibiting Egr_1 overexpression,but that is not the whole pharmacological mechanisms of F_2.