姜黄素改善缺氧缺血性脑损伤新生大鼠远期神经行为缺陷的机制  

The mechanism of curcumin improving long-term neurobehavioral deficits in neonatal rats with hypoxic-ischemic brain injury

作　　者：唐佳欣 耿佳庆 严彩霞[1] 方成志[1] 方芳[1] 张丙宏[1] Tang Jiaxin;Geng Jiaqing;Yan Caixia;Fang Chengzhi;Fang Fang;Zhang Binghong(Department of Neonatology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院新生儿科,430060

出　　处：《疑难病杂志》2024年第7期861-865,共5页Chinese Journal of Difficult and Complicated Cases

基　　金：中央引导地方科技发展专项资金[鄂财教发(2016)109];湖北省自然科学基金(WJ2019M184)。

摘　　要：目的探讨姜黄素减轻缺氧缺血性脑损伤新生大鼠相关神经炎性反应的作用机制并且评估其对缺氧缺血性脑损伤远期神经行为的影响。方法2023年1—6月在武汉大学人民医院中心实验室进行实验。选用7日龄新生SD大鼠66只,采用随机数字表法分为假手术组(n=22)、缺氧缺血脑损伤组(HIBD组,n=22)和缺氧缺血脑损伤+姜黄素组(HIBD+姜黄素组,n=22)。造模后24 h采用Longa评分评估造模是否成功,造模后48 h通过负性趋地反射、翻正反射评估短期神经行为;4周后采用圆筒实验、水迷宫实验、转角实验、爬杆实验评估远期神经行为;采用ELISA试剂盒检测脑组织炎性因子(TNF-α、IL-1β、IL-6)水平;采用Western-blot法检测脑组织蛋白(STAT3、p-STAT3)水平。结果造模24 h后,HIBD组(n=18)与HIBD+姜黄素组(n=15)新生大鼠Longa评分为1~3分提示造模成功。短期行为学评估表明,与HIBD组比较,HIBD+姜黄素组负性趋地反射和翻正反射时间缩短(P<0.05)。远期神经行为学评估表明,与HIBD组比较,HIBD+姜黄素组圆筒实验大鼠左前肢使用率明显增加、水迷宫实验穿越平台潜伏期缩短、穿越平台象限次数增加、转角实验右转得分率减少、爬杆实验中爬杆时间缩短(P<0.01)。ELISA检测显示,与HIBD组比较,HIBD+姜黄素组脑组织中TNF-α、IL-1β和IL-6水平下降(P<0.05)。蛋白免疫印迹技术显示,与HIBD组比较,HIBD+姜黄素组脑组织中p-STAT3/STAT3水平降低(P<0.01)。结论姜黄素可通过抑制STAT3磷酸化介导的神经炎性反应并改善缺氧缺血性脑损伤新生大鼠神经行为学缺陷。Objective To investigate the pathogenesis of curcumin in reducing the neuroinflammatory and evaluate the effect of curcumin on the long-term neurobehavior in neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods The experiment was conducted in the Central Laboratory of Renmin Hospital of Wuhan University from January to June 2023.A total of 59 seven-day-old Sprague-Dawley(SD)rats were selected and randomly divided into sham surgery group(n=15),hypoxic-ischemic brain damage group(HIBD,n=22),and hypoxic-ischemic brain damage+curcumin group(HIBD+curcumin,n=22)using a random number table method.The Longa score was to assess whether or not the model was successful established.Short-term neurobehavioral tests were assessed by negative geotaxis reflex and righting reflex at 48 h after modeling.The long-term neurobehavior were assessed by the cylinder test,morris water maze,corner turn test,and pole-climbing test at 4 weeks after modeling.The brain tissues were collected to detect the levels of inflammatory factors(TNF-α,IL-1β,and IL-6)were detected by Elisa kit and the protein levels(STAT3 and p-STAT3)were detected by Western blot.Results The Longa scores of 1-3 in neonatal rats in the HIBD group(n=18)and the HIBD+curcumin group(n=15)suggested successful modeling.The short-term neurobehavior tests showed that compared to the HIBD group,the HIBD+curcumin group had a shorter negative geotaxis reflex and righting reflex time(F/P=135.037/<0.001,86.711/<0.001).The long-term neurobehavioral tests revealed significant improvements in the HIBD+curcumin group compared to the HIBD group.The HIBD+curcumin group exhibited increased utilization of the left forelimb in the cylinder test,shortened latency stage to cross the platform in the water maze test,increased number of crossings in the platform quadrant,decreased scores in the corner test,and reduced climbing time in the pole test(F/P=55.671/<0.001,102.160/<0.001,61.455/<0.001,28.526/<0.001,51.643/<0.001).ELISA detection showed that compared with the HIBD group,the HI

关 键 词：缺氧缺血性脑损伤 姜黄素 STAT3 肿瘤坏死因子-α 白介素-1Β 神经行为学 

分 类 号：R722[医药卫生—儿科]