氟比洛芬酯预先给药对大鼠局灶性脑缺血再灌注损伤的影响

Effects of flurbiprofen axetil pretreatment on local cerebral ischemia-reperfusion injury in rats

目的探讨氟比洛芬酯预先给药对大鼠局灶性脑缺血再灌注损伤的影响。方法雄性SD大鼠72只，6～8周，体重240—275g，随机分为4组（n=18）：假手术组（SH组）、生理盐水对照组（NS组）、氟比洛芬酯6mg／kg组（F1组）、氟比洛芬酯12mg／kg组（F2组）。腹腔注射16％水合氯醛350mg／kg麻醉后，SH组仅暴露颈总动脉；NS组于缺血前10min经舌静脉缓慢注射生理盐水2ml；F1组和F2组分别于缺血前10min经舌静脉缓慢注射氟比洛芬酯6、12mg／kg。线栓阻断大脑中动脉2h，开放24h以制备大鼠局灶性脑缺血再灌注模型，于再灌注24h时处死大鼠，断头取脑，测定脑梗死体积，计算脑梗死体积比，免疫组化法检测海马COX-2蛋白表达、RT-PCR法检测海马COX-2 mRNA表达。结果与SH组比较，NS组海马COX-2蛋白、COX-2 mRNA表达上调，F1组和F2组海马COX-2蛋白表达下调（P〈0．01）；与NS组比较，F1组和F2组海马COX-2蛋白表达下调，F2组脑梗死体积比降低，海马COX-2 mRNA表达下调（P〈0．01）；与F1组比较，F2组脑梗死体积比降低，海马COX-2 mRNA、COX-2蛋白表达下调（P〈0．05或0．01）。结论氟比洛芬酯12mg／kg预先给药可通过抑制COX-2活性并下调COX-2表达减轻大鼠局灶件脑缺血再灌沣损伤。

Objective To investigate the effects of pretreatment with nonselective cyclooxygenase inhibitor-flurbiprofen axetil （FPA） on local cerebral ischemia-reperfusion （I/R） injury. Methods Seventy two 6-8 week old male SD rats weighing 240-275 g were randomly divided into 4 groups （ n = 18 each） ： group Ⅰ sham operation （SH）; groupⅡ normal saline ＋ local cerebral I/R （NS） and group Ⅲ , iv FPA 6/12 mg/kg ＋ local cerebral I/R （F1 , F2 ）. The animals were anesthetized with intraperitoneal 16% chloral hydrate 350 mg/kg. Right carotid artery was exposed. A nylon thread with rounded tip was inserted into internal carotid artery and threaded cranially until resistance was feh. In this way middle cerebral artery was occluded （MCAO） for 2 h followed by 24 h reperfusion. In group Ⅲ and Ⅳ FPA 6 and 12 mg/kg was injected iv at 10 min before ischemia respectively. The animals were killed at the end of 24 h reperfusion and their brains were removed for determination of infarct size （by TFC staining） and expression of COX-2 mRNA and protein in hippocampus. Results MCAO induced local cerebral infarct and up-regulated the expression of COX-2 mRNA and protein in hippocampus. The infarct size was significantly smaller and the expression of COX-2 mRNA and protein was significantly lower in group F2 than in group NS. Conclusion Pretreatment with FPA 12 mg/kg can protect the brain from local cerebral I/R injury induced by MCAO through inhibition of COX-2 mRNA and protein expression in rats.