异丙酚预先给药对大鼠局灶性脑缺血再灌注时脑组织p-JNK、MMP-9和AQP-4表达的影响  

Effect of propofol pretreatment on the expression of p-JNK, MMP-9 and AQP-4 during focal cerebral isch- emin-reperfusion in rats

作　　者：纪风涛[1] 曹铭辉[1] 梁建军[1] 苗利萍[1] 

机构地区：[1]中山大学孙逸仙纪念医院麻醉科,广州市510120

出　　处：《中华麻醉学杂志》2010年第11期1357-1360,共4页Chinese Journal of Anesthesiology

基　　金：基金项目：广东省自然科学基金（7001595）

摘　　要：目的 评价异丙酚预先给药对大鼠局灶性缺血再灌注时脑组织磷酸化c-Jun氨基末端蛋白激酶（p-JNK）、基质金属蛋白酶-9（MMP-9）和水通道蛋白-4（AQP-4）表达的影响.方法 健康成年雄性SD大鼠72只,体重250～280g,随机分成4组（n=18）：假手术组（S组）;脑缺血再灌注组（IR组）于缺血前30 min腹腔注射生理盐水10ml/kg;不同浓度异丙酚预先给药组（P1组和P2组）于缺血前30 min分别腹腔注射0.5%或1%异丙酚10 ml/kg.IR组、P1组和P2组采用线栓法建立大鼠局灶性脑缺血再灌注模型,缺血2 h,再灌注24 h.大鼠清醒后,进行神经功能缺陷评分.再灌注24 h时处死大鼠,处死前1 h股静脉注射2%伊文氏蓝（EB）溶液3 ml/kg,处死后取脑组织,测定含水量、EB含量、p-JNK、MMP-9和AQP-4的表达水平.结果 与S组比较,IR组、P1组和P2组神经功能缺陷评分、脑组织含水量和EB含量升高,p-JNK、MMP-9和AQP-4的表达上调（P＜0.05）;与IR组比较,P1组和P2组神经功能缺陷评分、脑组织含水量和EB含量降低,p-JNK、MMP-9和AQP-4的表达下调（P＜0.05）;与P1组比较,P2组脑组织p-JNK和MMP-9的表达下调（P＜0.05）,神经功能缺陷评分、脑组织含水量、EB含量和AQP-4表达差异无统计学意义（P＞0.05）.结论 异丙酚预先给药可通过抑制JNK信号通路的激活,抑制脑组织MMP-9和AQP-4的表达上调,减轻大鼠局灶性脑缺血再灌注损伤.Objective To investigate the effect of propofol pretreatment on the expression of phosphorylated c-Jun N-terminal kinase （p-JNK）, matrix metalloproteinase-9 （MMP-9） and aquaporin-4 （AQP-4） during focal cerebral ischemia-reperfusion （I/R） in rats. Methods Seventy-two healthy male SD rats weighing 250-280 g were randomly divided into 4 groups （n = 18 each）： sham operation group （group S）, I/R group and propofol pretreatment group （P1 and P2）. In group I/R, P1 and P2, focal cerebral I/R was induced by occlusion of middle cerebralartery for 2 h followed by 24 h of reperfusion. In group P1 and P2, intraperitioneal 0.5 % and 1% propofol 10 ml/kg were injected 30 rmin before ischemia respectively. In group I/R, normal saline 10 ml/kg was given instead of propofol 30 min before ischemia. Neurological deficit score （NDS） was assessed after consciousness was recovered. 2% Evans blue （EB） 3 ml/kg was injected intravenously 1 h before the animals were sacrificed at 24 h of reperfusion. The brain tissues were taken for determination of the brain water content, EB content and expression of p-JNK, MMP-9 and AQP-4. Results Compared with group S, the NDS and content of water and EB were significantly increased and the expression of p-JNK, MMP-9 and AQP-4 was up-regulated in group I/R, P1 and P2（P 〈 0.05）. Compared with group I/R, the NDS and content of water and EB were significantly decreased and the expression of p-JNK, MMP-9 and AQP-4 was down-regulated in group P1 and P2 （P 〈 0.05）. Compared with group P1 , the expression of p-JNK and MMP-9 was down-regulated （P 〈 0.05）, but no significant difference was found in the NDS, water and EB content and the expression of AQP-4 in group P2 （P 〉 0.05）. Conclusion Propofol pretreatment can reduce focal cerebral I/R injury by inhibiting the activation of JNK signal pathway and up-regulation of MMP-9 and AQP-4 expression.

关 键 词：二异丙酚 再灌注损伤 脑 JNK丝裂原活化蛋白激酶类 基质金属蛋白酶9 水通道蛋白质4 

分 类 号：R285.5[医药卫生—中药学]