基础医学与临床 ›› 2014, Vol. 34 ›› Issue (3): 381-385.

• 研究论文 • 上一篇    下一篇

P38抑制剂SB203580对大鼠脑缺血再灌注后AQP4 表达及脑水肿的影响

王耀辉,李国辉,袁微   

  1. 桂林医学院
  • 收稿日期:2013-07-01 修回日期:2013-09-24 出版日期:2014-03-05 发布日期:2014-02-27
  • 通讯作者: 李国辉 E-mail:qhdhh2011@163.com

P38 MAPK inhibitor SB203580 decreases the AQP4 expression and cerebral edema of rats after cerebral ischemia and reperfusion

  • Received:2013-07-01 Revised:2013-09-24 Online:2014-03-05 Published:2014-02-27

摘要: 目的 探讨P38丝裂原活化蛋白激酶(MAPK)抑制剂SB203580对大鼠脑缺血再灌注后脑组织水通道蛋白4(AQP4) 表达及脑水肿的影响。方法 SPF 级雄性SD 大鼠54只,随机分为假手术组(sham组)、模型组(I/R组)和P38抑制剂组(SB203580组)。用线栓法制备大鼠局灶性脑缺血再灌注模型。模型组与P38抑制剂组分别于造模前15 min舌下静脉注射10%二甲基亚砜(DMSO,400 μg/kg)和P38抑制剂(SB203580,400 μg/kg)。缺血2 h再灌注24 h后对大鼠进行神经功能缺损评分,采用HE染色观察大鼠脑组织病理改变,干湿比重法测定缺血半球的脑含水量,Western blot 检测磷酸化P38(p-P38) 和AQP4 蛋白的表达、RT-PCR法检测AQP4 mRNA的表达。结果 与I/ R组相比,SB203580组大鼠神经功能缺损症状明显改善,缺血侧半球脑含水量明显降低(P<0.05)。I/ R组大鼠缺血周边区脑组织p-P38 、AQP4蛋白 及mRNA 的表达分别为2.463±0.138、2.660±0.130及1.065±0.125,高于SB203580组的1.653±0.105、1.771±0.092及0.552±0.069 (P<0.05)。结论 P38抑制剂SB203580减轻大鼠脑缺血再灌注后AQP4表达及脑水肿,其机制可能与SB203580抑制P38信号通路的激活降低了下游AQP4的表达有关。

关键词: 脑缺血再灌注 , 脑水肿 , 水通道蛋白4 , p38, SB203580

Abstract: Objective To investigate the role of P38 inhibitor SB203580 on cerebral edema and Aquaporin 4(AQP4) expression after cerebral ischemia reperfusion in rats. Methods Fifty-four SPF male Sprague-Dawley rats weighing 240-260 g were randomly divided into 3 groups: sham operation group(sham grope); ischemia reperfusion group(I/R group); P38 inhibitor group(SB203580 group).The focal ischemia reperfusion rat model was established by the modified suture method. The rats of I/R group and SB203580 group were exposed to DMSO(10%,400μg/kg) or P38 inhibitor SB203580(400μg/kg) 15 min before suffered from cerebral ischemia. Neurologic function was scored at 24 h reperfusion after 2 h ischemia. HE staining was used to examine brain tissue injury, wet-dry ratio was measured to estimate cerebral edema, Western blot was used to detect the expression of p-P38 and AQP4, RT-PCR was used to detect AQP4mRNA. Results P38 inhibitor SB203580 could improve behavioral scores of ischemic reperfusion rats. The brain water content was decreased after SB203580 treatment compared with I/R group(0.792±0.010 vas 0.817 ± 0.012). The expression of p-P38, AQP4 and AQP4mRNA in margin of infarction of SB203580 group are decreased compared with I/R group compared with I/R group . Conclusion P38 inhibitor SB203580 alleviate the AQP4 expression and cerebral edema in cerebral ischemia reperfusion rats through P38 MAPK pathway.

Key words: Cerebral ischemia reperfusion, cerebral edema, aquaporin 4, p38, SB203580

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