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,400μg/kg)和P38抑制剂(SB203580,400μg/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。
Objective To explore the role of P38 inhibitor SB203580 on cerebral edema and Aquaporin 4 （AQP4） expression after cerebral isehemia 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% ,400 μg/kg） or P38 inhibitor SB203580（400 μg/kg） 15 min before suffered from cerebral ischemia. Neu rologic function was scored at 24 h reperfusion after 2 h ischemia. HE staining was used to examine brain tissue in jury, 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 AQP4 mRNA. Results P38 inhibitor SB203580 improved behavioralscores of ischemic reperfusion rats. The brain water content was decreased after SB203580 treatment compared with I/R group（0. 792 ±0. 010 vs O. 817 ±0. 012）. The expression of p-P38, AQP4 and AQP4 mRNA in margin of in- farction of SB203580 group are decreased as compared with I/R group compared with I/R group. Conclusions P38 inhibitor SB203580 alleviates AQP4 expression and cerebral edema in cerebral ischemia reperfusion rats through P38 MAPK pathway.
出处
《基础医学与临床》
CSCD
北大核心
2014年第3期381-385,共5页
Basic and Clinical Medicine
