碘化N-正丁基氟哌啶醇对心肌细胞缺氧复氧损伤保护作用机制的研究

The Protective Effect of N-n-butyl Haloperidol Iodide on Hypoxia/Reoxygenation Injury of Cardiocytes

目的：探讨碘化N-正丁基氟哌啶醇（F2）对缺氧复氧心肌细胞损伤及早期生长反应基因-1（Egr-1）蛋白表达的影响。方法：用1—3d的SD大鼠进行心肌细胞原代培养。取生长5-6d的心肌细胞分为对照组、缺氧复氧组、聚乙二醇＋脂质体组、反义寡核苷酸组、反义寡核苷酸＋F2组。除对照组外其他组均做缺氧复氧模型。通过测定肌酸激酶、乳酸脱氢酶、肌钙蛋白、超氧化物歧化酶、丙二醛及肿瘤坏死因子-α的变化，观察心肌细胞损伤及炎症反应情况：Westernblot法检测培养心肌细胞中Egr-1蛋白的表达水平。结果：与对照组比，反义寡核苷酸组及反义寡核苷酸＋F2组Egr-1蛋白表达明显减少（P（0．05），细胞损伤及炎症反应程度明显减弱（P〈0．01）；反义寡核苷酸组与反义寡核苷酸＋F2组比，Egr-1蛋白表达虽无统计学意义（P〉0．05），但细胞损伤及炎症反应改善情况却有统计学意义（P〈0．05）。结论：F2可通过抑制Egr-1蛋白表达来减轻缺氧复氧心肌细胞的损伤，它还可通过其他机制起到保护缺氧复氧心肌细胞损伤的作用。

Objective： To study the effects of N-n-butyl haloperidol iodide（F2）on early＇growth response gene-l（Egr-1 ）protein expression in cultured cardiocytes after hypoxia/reoxygenation. Methods： The cardiocytes from neonatal SD rats were isolated and cultured. The hypoxia/reoxygenation models of neonatal rat cardiocytes were established. The cardiocytes were randomly divided into control group, hypoxia/reoxygenation group, Macrogol and Lipfectemine group, antisense nucleotide group, antisense nucleotide and F2 group. Levels of creatinkinase, lactic acid dehydrogenase, troponin, superoxide dismutase, malondialdehyde, turnout necrosis factor-α were determined. The expression levels of Egr-1 protein in cardiocytes were examined by Western blot. Results： Compared with the control group, antisense nucleotide group and antisense nucleotide and F2 group could inhibit the expression levels of Egr-1 protein（ P 〈 0.05）, but there was no difference between antisense nucleotide group and antisense nucleotide and F2 group（ P 〉 0.05）. Conclusion： F2 can protect cardiocytes from hypoxia/reoxygenation injury by inhibiting Egr-1 overexpression, but that is not the whole molecular mechanisms of F2.