丁咯地尔对脑缺血再灌注损伤大鼠脑组织MMP-9与TIMP-1的影响

目的:观察丁咯地尔对大鼠脑缺血再灌注后基质金属蛋白酶-9(MMP-9)与基质金属蛋白酶抑制剂-1(TIMP-1)表达的影响,探讨丁咯地尔的脑保护作用机制.方法:健康SD大鼠108只随机分成假手术组、对照组和丁咯地尔治疗组,每组36只,18只用于检测MMP-9、TIMP-1,18只测量脑组织含水量.大鼠建立脑缺血再灌注损伤模型,缺血时间为1 h,假手术组仅在颈外动脉处穿线;对照组制作脑缺血再灌注模型,不作干预;丁咯地尔治疗组于再灌注时经尾静脉给药(赛来乐3 ml/kg,每ml含丁咯地尔10 mg).分别于再灌注后1 d、2 d和3 d处死,每个时间点6只大鼠,断头取脑,以干湿重法测量缺血侧脑组织含水量;用免疫组化方法检测MMP-9与TIMP-1阳性细胞的表达情况.结果:在各时间点丁咯地尔治疗组脑组织含水量低于对照组,丁咯地尔治疗组MMP-9细胞阳性率低于对照组,而TIMP-1细胞阳性率仅在再灌注后第3 d时高于对照组(P＜0.05).结论:丁咯地尔可能通过调节MMP-9/TIMP-1表达,发挥抗脑水肿作用.

Effect of buflomedil on MMP-9 and TIMP-1 after cerebral ischemiareperfusion in rats

Aim: To investigate the effect of buflomedil on the expression of MMP-9 and TIMP-1 after cerebral ischemia/reperfusion (I/R) injury in rats. Methods: A total of 108 healthy,male SD rats were randomly divided into sham-operation group, operation group and buflomedil treatment group. Rat transient cerebral ischemic injury model was established with suture emboli method. Six rats were sacrificed at 1 d, 2 d and 3 d, respectively after reperfusion. The brain water content was examined. The expression of MMP-9 and TIMP-1 was detected using immunohistochemical method. Results: The brain water content of buflomedil treatment group was lower than that of the control group. The number of the activated MMP-9 immunoreactive cells of buflomedil treatment group was lower than that of the control group at 3 time points. The number of the activated TIMP-1 immunoreactive cells of buflomedil treatment group was higher than that of the control group at 3 d after reperfusion, P< 0.05 . Conclusion: Buflomedil has the function against cerebral edema by accommodating MMP-9/TIMP-1.