姜黄素预先给药对肠缺血再灌注大鼠肺损伤时iNOS活性的影响

Effects of curcumin pretreatment on iNOS activity during lung injury induced by intestinal ischemia-reperfusion in rats

目的 评价姜黄素预先给药对肠缺血再灌注大鼠肺损伤时诱导型一氧化氮合酶（iN-OS）活性的影响.方法 健康清洁级雌性SD大鼠24只,体重180～220 g,采用随机数字表法分为3组（n=8）：假手术组（Sham组）、肠缺血再灌注组（H/R组）和姜黄素预先给药组（Cur组）.采用夹闭肠系膜上动脉75 min后再灌注的方法制备肠缺血再灌注诱发大鼠肺损伤模型.于模型制备前5dCur组每天胃饲姜黄素200 mg/kg（采用生理盐水稀释）,Sham组和H/R组胃饲等容量生理盐水.于再灌注4h时放血处死大鼠,取肺组织标本,称重,计算肺湿/干重（W/D）比值,光镜下观察病理学结果并行肺组织损伤评分,采用硝酸还原酶法测定NO含量,采用比色法检测iNOS的活性.结果 与Sham组比较,H/R组和Cur组大鼠肺组织损伤评分、W/D比值、NO含量及iNOS活性升高（P＜0.05）;与H/R组比较,Cur组大鼠肺组织损伤评分、W/D比值、NO含量和iNOS活性降低（P＜0.05）.Cur组肺组织病理学损伤程度较H/R组明显减轻.结论 姜黄素预先给药减轻肠缺血再灌注大鼠肺损伤的机制与其降低iNOS活性有关.

Objective To evaluate the effects of curcumin pretreatment on the activity of inducible nitric oxide synthase （iNOS） during lung injury induced by intestinal ischemia-reperfusion （Ⅰ/R） in rats.Methods Twenty-four pathogen-free female Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups （n =8 each） using a random number table：sham operation group （group Sham）;intestinal Ⅰ/R group （group Ⅱ/R）;curcumin pretreatment group （group Cur）.A rat model of lung injury induced by intestinal Ⅰ/R which was produced by occlusion of superior mesenteric artery for 75 min followed by reperfusion was established.At 5 days before Ⅰ/R,curcumin 200 mg/kg （in 20 mg/ml of normal saline） was given through a gastric tube in group Cur,while the equal volume of normal saline was given instead in Sham and Ⅱ/R groups.The rats were sacrificed at 4 h of reperfusion,and the pulmonary specimens were obtained for determination of wet/dry lung weight ratio （W/D ratio）,NO content （by using nitrate reductase method） and iNOS activity （using colorimetric method） and for examination of pathological changes （with light microscope）.The pathological changes of the lung were scored.Results Compared with group Sham,the pathological scores,W/D ratio,NO content and iNOS activity were significantly increased in Ⅱ/ R and Cur groups.Compared with Ⅱ/R group,the pathological scores,W/D ratio,NO content and iNOS activity were significantly decreased in group Cur.The pathological changes of lungs were significantly attenuated in group Cur as compared with H/R group.Conclusion The mechanism by which curcumin pretreatment attenuates lung injury induced by intestinal Ⅰ/R is related to decrease in iNOS activity in rats.