摘要
目的探讨p38 MAPK在大鼠脑缺血再灌注后脑组织AQP4表达及脑水肿形成中的作用。方法 54只SPF级雄性SD大鼠,体质量240～260g,随机分为假手术组(sham组)、缺血再灌注组(I/R组)和p38抑制剂组(SB组)。采用改良线栓法制备大鼠大脑中动脉缺血/再灌注(MCAO/R)模型。I/R组、SB组分别于造模前15min舌下静脉注射10%DMSO和p38特异性抑制剂SB203580。sham组不作脑梗死。缺血2h再灌注24h对大鼠进行神经功能缺损评分,采用干湿比重法测定缺血半球脑含水量、Western blot检测缺血周边区脑组织磷酸化p38和AQP4表达。结果 (1)与sham组相比,I/R组大鼠神经功能缺损加重(P<0.05);与I/R组相比,SB组大鼠神经功能缺损减轻(P<0.05)。(2)与sham组相比,I/R组大鼠缺血周边区脑组织磷酸化p38的水平上升(P<0.05),AQP4的表达上调(P<0.05),缺血侧半球脑含水量升高(P<0.05);与I/R组相比,SB组大鼠缺血周边区脑组织磷酸化p38的水平下降(P<0.05),AQP4的表达下调(P<0.05),缺血侧半球脑含水量降低(P<0.05)。结论 p38 MAPK参与了大鼠脑缺血再灌注后AQP4表达上调及脑水肿形成,抑制p38 MAPK的激活可降低AQP4表达的上调和减轻脑水肿。
Objective To investigate the role of p38 MAPK on cerebral edema and Aquaporin-4（AQP4） expression after cerebral ischemia reperfusion in rats.Methods Fifty-four SPF male SD rats weighing 240 ～ 260g were randomly divided into 3 groups： sham operation group（sham group）;ischemia reperfusion group（group I/R）;p38 inhibitors group（group SB）.The middle cerebral artery ischemia/reperfusion rats model was established by the suture method with some modification.The group I/R and group SB rats were exposed to 10% DMSO and SB203580 for 15min before suffered from cerebral ischemia.The neurologic exams were assessed at 24h after reperfusion,the rats were sacrificed after anesthetization.To estimate cerebral edema,the wet-dry ratio was measured.Western blot was used to detect the expression of p-p38 and AQP4 in the infarct region.Results（1） The neurologic function deficit was serious in group I/R and group SB compared to Sham group（P 0.05）.（2） I/R caused enhanced expression of p-p38 protein and this effect was blocked by SB203580.AQP4 protein expression increased after I/R（P 0.05） and the ischemic hemisphere cerebral edema was increased compared with Sham group（P 0.05）.Application of the SB203580 depressed AQP4 up-regulation（P 0.05） and cerebral edema of ischemic hemisphere was lower in the SB group（P 0.05）.Conclusion p38MAPK signaling pathway participates in brain edema after cerebral ischemia-reperfusion in rat and blocking this pathway can attenuate AQP4 up-regulation and mitigate the cerebral edema.
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2013年第8期700-702,共3页
Journal of Apoplexy and Nervous Diseases
