碘化N-正丁基氟哌啶醇对大鼠心脏微血管内皮细胞缺氧复氧损伤保护机制的研究

N-n-butyl haloperidol iodide protects rat cardiac microvascular endothelial cells from anoxia and reoxygenation injury

目的观察碘化Ⅳ.正丁基氟哌啶醇（N-n-butylhalo-peridol iodide，F2）对培养的内皮细胞缺氧／复氧（anoxia／reoxygenation，A／R）损伤及早期生长反应基因-1（early growth response gene1，Egr-1）蛋白表达的影响。方法应用新生SD大鼠进行心脏微血管内皮细胞（cardiacmicrovas．eularendothelialcells，CMECs）原代培养，取3-4代的CMECs建立A／R模型。通过测定细胞培养上清液中乳酸脱氢酶（LDH）及CMECs中超氧化物歧化酶（SOD）、丙二醛（MDA）含量，观察CMECs损伤程度；应用ELISA法测定细胞培养上清液肿瘤坏死因子-d（TNF-α）的含量，观察CMECs炎症反应水平；Westernblot法检测培养CMECs中Egr一1的蛋白表达水平。结果A／R造成CMECs内MDA升高，SOD下降，上清液中LDH、TNF—α含量升高，A／R刺激下细胞Egr-1的蛋白表达水平明显升高；A／R刺激前给予F2：可减轻CMECs的损伤及炎症反应程度，抑制Egr-1蛋白的表达。结论F：对心脏微血管内皮细胞A／R损伤具有保护作用，该作用可能与其抑制Egr-1的表达有关。

Aim To investigate the effects of N-n-bu- tyl haloperidol iodide （F2 ） on Egr-1 protein expression in cultured endothelial cells after anoxia/reoxygenation （A/R）. Methods The cardiac mierovascular endo- thelial ceils （CMECs） were cultured from SD neonatal rat, Experiments were performed between passages 3 and 4 for preparation of A/R model. Levels of lactate dehydrogenase （ LDH ）, superoxide dismutase （SOD）, malondialdehyde （MDA）, and tumor necro-sis factor-~ （TNF-ct） were measured. The expression levels of Egr-1 protein in CMECs were examined by Western blot. Results The CMECs treated with A/Rwere damaged the increase of as evidenced by the decrease of SOD, MDA, LDH and TNF-o~ level, and the expression of Egr-1 protein of the cells increased markedly. Compared with the A/R group, F2 could in-hibit the expression of Egr-1 protein, and protect CMECs from A/R injury. Conclusion F2 can protect cultured CMECs from A/R injury, which might be as- sociated with the inhibition of Egr-1 overexpression.