乌司他丁对术前睡眠剥夺老龄大鼠术后认知功能障碍的影响

Effect of ulinastatin on postoperative cognitive dysfunction in preoperative sleep deprived aged rats

目的 评价乌司他丁对术前睡眠剥夺老龄大鼠术后认知功能障碍的影响.方法 清洁级健康雄性SD大鼠60只,18月龄,体重350～ 500 g,采用随机数字表法分为3组（n=20）：对照组（C组）、术前睡眠剥夺组（D组）和乌司他丁组（U组）.D组和U组术前采用多平台水环境法制备大鼠睡眠剥夺模型,随后3组均行脾切除术.U组于睡眠剥夺前和术毕即刻腹腔注射乌司他丁100U/g.于术后3d时随机取10只大鼠处死取海马,采用ELISA法测定IL-1β、IL-6和TNF-α含量.每组余10只大鼠术后3～7d行Morris水迷宫实验,记录逃避潜伏期和原平台位置停留时间.结果 与C组比较,D组和U组术后第4～6天逃避潜伏期延长,原平台位置停留时间缩短,术后3d时海马IL-1β、IL-6和TNF-α含量升高（P＜0.05）;与D组比较,U组术后第4～6天逃避潜伏期缩短,原平台位置停留时间延长,术后3d时海马IL-1β、IL-6和TNF-α含量降低（P＜0.05）.结论 乌司他丁可减轻术前睡眠剥夺老龄大鼠术后认知功能障碍,与其抑制炎症反应有关.

Objective To evaluate the effect of ulinastatin on postoperative cognitive dysfunction in preoperative sleep deprived aged rats.Methods Sixty clean healthy male Sprague-Dawley rats,aged 18 months,weighing 350-500 g,were divided into 3 groups （n=20 each） using a random number table：control group （group C）,sleep deprivation group （group D） and ulinastatin group （group U）.Sleep deprivation was induced by using modified multiple platform method in D and U groups,and then splenectomy was performed in three groups.Ulinastatin 100 U/g was intraperitoneally injected before sleep deprivation and immediately after operation in group U.Ten rats were randomly selected at 3 days after operation and sacrificed,and hippocampi were removed for determination of the contents of interleukin-1β （IL-1β）,IL-6 and tumor necrosis factor-α （TNF-α） by enzyme-linked immunosorbent assay.Morris water maze test was performed at 3-7 days after operation in the rest ten rats in each group,and the escape latency and time of staying at the original platform were recorded.Results Compared with group C,the escape latency was significantly prolonged at 4-6 days after operation,the time of staying at the original platform was shortened,and the contents of IL-1β,IL-6 and TNF-α were increased at 3 days after operation in D and U groups （P〈0.05）.Compared with group D,the escape latency was significantly shortened at 4-6 days after operation,the time spent in the original platform was prolonged,and the contents of IL-1β,IL-6 and TNF-α were decreased at 3 days after operation in group U （P〈0.05）.Conclusion Ulinastatin can mitigate postoperative cognitive dysfunction in preoperative sleep deprived aged rats,which is related to inhibiting inflammatory responses.