辛醇对大鼠脑缺血再灌注后基质金属蛋白酶-9组织型金属蛋白酶抑制剂-1表达及脑水肿的影响

摘要

Objective To investigate the treatment of octanol on matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein expression,cerebral water content,infarction volume after ischemia-reperfusion in rats.Methods 150 SD rats were randomly divided into sham operated group (n=24),MCAO group (n=24),DMSO solvent control group (n=24) and octanol treatment group (n=24).A model of middle cerebral artery occlusion was induced by suture method.TTC stain was used to detect the infarction volume,dry-wet weight method to determine the brain water content.The expression of MMP-9 and TIMP-1 protein was detected by immunofiuorescence and Western blot.Results At 24 h of reperfusion after ischemia for 2 h,the octanol treatment group compared with MCAO group brain infarction volume obviously decreased(P＜0.05),water content significantly reduced ((78.16± 1.47) ％ vs (80.88±0.73) ％,P＜0.05),the number of MMP-9 positive cells obviously decreased((10.67±2.16) vs (29.00±3.40),P＜0.05),the expression of MMP-9 protein significantly reduced ((0.14±0.01) vs (0.21±0.02),P＜0.05)and the number of TIMP-1 positive cells significantly increased ((27.83 ±2.13) vs (5.67± 1.03),P＜0.05),the expression of TIMP-1 protein obviously increased((0.42±0.01) vs (0.28± 0.01),P＜0.05).The difference between MCAO group and DMSO solvent control group was not statistically significant(P ＜0.05).Conclusion Octanol may reduce brain edema,brain infarction volume.Up-regulation the expression of MMP-9 and down-regulation the expression of TIMP-1 may be one of the underlying mechanisms of the octanol neuroprotection.%目的 探讨辛醇对大鼠局灶性脑缺血再灌注后基质金属蛋白酶-9(MMP-9),组织型金属蛋白酶抑制剂-1(TIMP-1)的表达与其对脑水肿的影响,以及辛醇脑保护的可能机制.方法 雄性SD大鼠按随机数字表法分为假手术组(n=24),手术组(n=24),DMSO溶剂对照组(n=24),辛醇治疗组(n=24).线栓法制备大脑中动脉缺血模型,于缺血2h/再灌注24 h,分别采用TTC法检测脑梗死体积,干湿重法测定脑组织含水量,免疫荧光法检测MMP-9、TIMP-1阳性细胞数,Westernblot法检测MMP-9、TIMP-1蛋白的表达.结果 在缺血2h/再灌注24 h条件下,辛醇治疗组与手术组相比脑梗死体积显著减少(P＜0.05),脑组织含水量明显降低[(78.16±1.47)％ vs (80.88±0.73)％,P＜0.05],MMP-9阳性细胞数显著减少[(10.67±2.16)个/视野vs (29.00±3.40)个/视野,P＜0.05],MMP-9蛋白表达明显降低[吸光度(A)值:(0.14±0.01)vs (0.21±0.02),P＜0.05],TIMP-1阳性细胞数显著增加[(27.83±2.13)个/视野vs (5.67±1.03)个/视野,P＜0.05],TIMP-1蛋白表达明显增多[吸光度(A)值:(0.42±0.01)vs (0.28±0.01),P＜0.05],手术组与溶剂对照组相比,各指标无显著差异(P＞0.05).结论 辛醇的应用能减轻脑水肿,减少脑梗死体积,对脑组织起到保护作用;通过调节MMP-9、TIMP-1的表达可能是辛醇对脑组织的保护机制之一.