p38丝裂原活化蛋白激酶途径对大鼠脑缺血再灌注后脑组织基质金属蛋白酶-9表达及脑水肿形成的影响

Effect of p38 mitogen-activated protein kinase on expression of matrix metalloproteinase-9 and formation of cerebral edema in rats with cerebral ischemia-reperfusion

目的探讨p38丝裂原活化蛋白激酶(MAPK)途径对大鼠脑缺血再灌注后脑组织基质金属蛋白酶-9(MMP-9)表达及脑水肿形成的影响。方法 54只SPF级雄性SD大鼠,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模型。再灌注24 h后对大鼠进行神经功能缺损评分,Evans Blue法测定血-脑屏障通透性;干湿比重法测定脑组织含水量,采用Western blot检测缺血周边区脑组织磷酸化p38(p-p38)和MMP-9的表达。结果与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明显减轻(P<0.05)。与Sham组比较,I/R组血-脑屏障通透性及脑含水量明显增加(均P<0.05);与I/R组相比,SB组血-脑屏障通透性及脑含水量降低(均P<0.05)。与Sham组相比,I/R组大鼠缺血周边区脑组织p-p38、MMP-9的表达明显上调(均P<0.05);与I/R组相比,SB组大鼠缺血周边区脑组织p-p38、MMP-9的表达明显下调(均P<0.05)。结论 p38 MAPK参与了大鼠脑缺血再灌注后脑水肿的形成,机制可能为大鼠脑缺血再灌注后激活p38MAPK使缺血周边区脑组织MMP-9的表达上调,破坏血-脑屏障通透性,导致脑水肿发生。

Objective To investigate the effect of p 38 mitogen-activated protein kinase （ MARK） on expression of matrix metalloproteinase-9（MMP-9） and formation of cerebral edema in rats with cerebral ischemia-reperfusion. Methods Fifty-four SPF male SD rats were randomly divided into sham operation group （ Sham group ） , ischemia-reperfusion group（I/R group） and p38 inhibitor group（SB group）.Middle cerebral artery ischemia-reperfusion model was made by modified line plug method .The neurologic exams were assessed at 24 h after reperfusion , Evans Blue method was used tomeasurement Blood-brain barriers permeability,the wet-dry ratio was used to measured to estimate cerebral edema ,Western blot was used to detect the expression of phosphorylation p 38 （ p-p38 ） and MMP-9 in the infarct region .Results Compared with Sham group , I/R group had aggravated neurological deficits （ P〈0.05 ）;compared with the I/R group, SB group had alleviate neurological deficits （P〈0.05）.Compared with Sham group, blood-brain barrier permeability and brain water content of I /R group were significantly increased （ all P〈0.05 ）;compared with the I/R group, blood-brain barrier permeability and brain water content of SB group were significantly decreased（all P〈0.05）.Compared with Sham group , the expression of p-p38, MMP-9 in margin of ischemia of I/R group were significantly increased （all P〈0.05）;compared with the I/R group, the expression of p-p38, MMP-9 in margin of ischemia of SB group were significantly decreased （all P〈0.05）.Conclusions p38 MAPK involved in the formation of brain edema in rats with cerebral ischemia-reperfusion , and its mechanism may be cerebral ischemia-reperfusion activates p38MAPK,and it make the expression of MMP-9 in margin of ischemia up-regulated,damaging blood-brain barrier permeability ,leading to cerebral edema .