乌司他丁对大鼠局灶性脑缺血再灌注时水通道蛋白4表达的影响

Effect of ulinastatin on expression of aquaporin-4 during cerebral ischemia-reperfusion in rats

目的评价乌司他丁对大鼠局灶性脑缺血再灌注时水通道蛋白4（AQP4）表达的影响。方法成年雄性sD大鼠135只，体重230～280g，采用随机数字表法，将其分为3组（n=45）：假手术组（S组）、局灶性脑缺血再灌注组（I／R组）和乌司他丁组（u组）。采用线栓法阻塞大脑中动脉2h恢复灌注的方法制备大鼠脑缺血再灌注损伤模型，u组于再灌注即刻尾静脉注射乌司他丁10万U／kg，S组和I／R组给予等容量生理盐水。于再灌注6、24和48h时处死大鼠，取脑组织，采用Trc染色法测定脑梗死体积，计算脑梗死体积比，干湿比重法测定脑含水量，免疫组化法测定AQP4表达。结果与s组比较，I／R组和U组各时点脑梗死体积比和脑含水量升高，AQP4表达上调（P〈0．05）；与I／R组比较，U组各时点脑梗死体积比和脑含水量降低，AQP4表达下调（P〈0．05）。结论乌司他丁减轻大鼠局灶性脑缺血再灌注损伤的机制与下调脑组织AQP4表达有关。

Objective To evaluate the effect of ulinastatin on the expression of aquaporin-4 （AQP4） during focal cerebral ischemia-reperfusion （I/R） in rats. Methods One hundred and thirty-five male adult Sprague- Dawley rats, weighing 230-280 g were randomly divided into 3 groups （ n = 45 each） ： sham operation group （S group）, I/R group and ulinastatin group （group U）. The rats were anesthetized with intrapefitoneal 10% chloral hydrate 3.5 ml/kg. Focal cerebral isehemia was induced by 2 h middle cerebral artery occlusion followed by 24 reperfusion. In U group, ulinastatin 100000 U/kg was injected immediately after beginning of reperfusion, while the equal volume of normal saline was injected in S and I/R groups. The rats were sacrificed at 6, 24 and 48 h of reperfusion and brains were removed for determination of infraet volume （by TIC）, brain water content and expres- sion of AQP4 （by immunohistoehemistry） in brain tissues. Results Compared with S group, the infarct volume and brain water content were significantly increased, and the expression of AQP4 was up-regulated at each time point in I/R and U groups （ P 〈 0.05）. Compared with I/R group, the infarct volume and brain water content were significantly decreased, and the expression of AQP4 was down-regulated at each time point in U group （ P 〈 0.05）. Conclusion The mechanism by which ulinastatin mitigates focal cerebral I/R injury is related to down-reg- ulation of AQP4 expression in brain tissues.