大鼠脑出血后基质金属蛋白酶的动态表达及七叶皂苷钠对其表达的影响

目的 观察大鼠脑出血(ICH)后基质金属蛋白酶-2( MMP-2)、MMP-9蛋白动态表达及其与血肿周围脑组织含水量的关系,以及观察七叶皂苷钠对MMP-2、MMP-9表达的影响.方法 Wistar大鼠250只随机分为4组:正常对照组10只、假手术组、ICH组和七叶皂苷钠治疗组各80只,于制模后6 h、12 h、24 h、48 h、72 h、120 h、7 d、15 d 8个时间点,测定各组血肿周围脑组织含水量、MMP-2和MMP-9的蛋白表达.结果 治疗组神经功能缺损较ICH组明显改善,尤以6 h～7 d时明显(P<0.01～0.05);6～120 h各治疗组血肿周围脑组织含水量较ICH组明显减少(P<0.01～0.05);ICH后MMP-2蛋白表达在6 h达到高峰,12 h时下降,与正常对照组相比具有统计学意义 (均P<0.01),治疗组MMP-2蛋白表达在各时间点较ICH组明显减少(均P<0.01);ICH后MMP-9蛋白表达在6 h开始上升,24～48 h达高峰,72 h时下降,与正常对照组相比,具有统计学意义(均P<0.01),其表达水平与血肿周围脑组织含水量呈正相关 (r=0.949, P<0.05);治疗组MMP-9蛋白表达在各时间点较ICH组明显减少(均P<0.01).结论 大鼠ICH后MMP-2、MMP-9蛋白的表达是ICH后早、中期脑水肿形成主要因素,七叶皂苷钠能降低MMP-2、MMP-9蛋白表达和脑组织含水量,对ICH具有保护作用.

Dynamic expression of matrix metalloproteinase and the effect of sodium aescine in rats with intracerebral hemorrhage

Objective To observe the relationship between dynamic expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 protein and water contents in perihematoma, and the effect of sodium aescine in rats with intracerebral hemorrhage(ICH). Methods 250 Wistar rats were assigned randomly to four groups: normal control group (10 rats), sham operation group (80 rats), ICH group (80 rats) and sodium aescine treating group (80 rats). The water contents in perihematom and the expressions of MMP-2 and MMP-9 protein were measured respectively at 6 h, 12 h, 24 h, 48 h, 72 h, 120 h, 7 d and 15 d after operation in each group. Results Neurological function deficit in sodium aescine treating group was improved compared with ICH group in 6 h~7 d (P<0.01~0.05). The water contents in perihematoma in treating group were reduced than in ICH group at 6 h~120 h (P<0.01~0.05). The expression of MMP-2 protein in ICH group peaked at 6 h, and decreased at 12 h, it was significantly different from normal control group (all P<0.01). The expression of MMP-2 protein in treating group was reduced than in ICH group at different time point (all P<0.01), and the expression of MMP-9 protein increased at 6 h, peaked at 24 h~48 h, and decreased at 72 h, the change had statistic significance compared with normal control group (all P<0.01). These expressions of MMP-9 protein were positively correlated with water contents in perihematoma (r=0.949, P<0.05). The expression of MMP-9 protein in treating group was reduced than in ICH group at different time point (all P<0.01). Conclusions The expression of MMP-2 and MMP-9 protein plays important roles in the brain edema at early and middle period after ICH. Sodium aescine may reduce the expression of MMP-2 and MMP-9 protein and decrease water contents in perihematoma. This drug may have protective effect to ICH.