黄体酮对局灶性脑缺血大鼠脑组织MMP-9和Ⅳ型胶原表达的影响

Effect of progesterone on the expressions of MMP-9 and collagen Ⅳ after focal cerebral ischemia in rats

目的:观察黄体酮对脑梗死大鼠脑组织基质金属蛋白酶9(MMP-9)和Ⅳ型胶原(collagenⅣ)表达水平的影响。方法:用线栓法制作大脑中动脉局灶性脑缺血模型(pMCAO),将成模大鼠随机分成模型组、环糊精(HBC)溶剂治疗组和黄体酮治疗组,每组设12、24、48及72h4个时间点,每个时间点6只大鼠,另选6只大鼠作为假手术组。用免疫组织化学技术检测各组大鼠脑组织MMP-9蛋白和collagenⅣ的表达情况。结果:脑梗死发生后大鼠脑组织MMP-9蛋白的表达水平均明显升高,经黄体酮治疗后其表达水平有所下降;4组间在不同时间点比较,差异均有统计学意义(P<0.05)。collagenⅣ的表达随着缺血时间的延长而逐渐减少,经黄体酮治疗后其丢失程度有所减轻;4组间在不同时间点比较,差异均有统计学意义(P<0.05)。结论:黄体酮可通过抑制MMP-9的表达、减少collagenⅣ的降解来减轻脑水肿。

Aim：To investigate the influence of progesterone（PROG） on the expression of MMP-9 and collagen Ⅳ after focal cerebral ischemia in rats.Methods：Rat permanent middle cerebral artery occlusion （pMCAO） model was used in this experiment. All rats were randomly divided into four groups： sham operated group,ischemic group, vehicle （HBC）-treated group and PROG-treated group. Except for shamed operated group, 6 rats were killed in each group at 12,24,48 and 72 h post-occlusion, respectively. Immunohistochemistry technique was used to detect the expressions of MMP-9 and collagen Ⅳ.Results：The expression level of MMP-9 protein was higher in ischemic group and vehicle （HBC）-treated group than other two groups after stroke. There is significant difference between this four groups at all time points （P0.05）. In addition, this study also revealed that the expression of MMP-9 protein was obviously down-regulated when compared with the ischemic group and the HBC treated group at all time points （P0.05）. In the ischemic group the expression of collagen Ⅳ gradually decreased with time prolonging. There is significant difference between this four groups at all time points （P0.05）. In the progesterone treated group, the degradation of collagenⅣ protein was obviously reduced when compared with the ischemic group at all time points （P0.05）.Conclusion：Progesterone significantly reduced the expression of MMP-9 and block the down regulation of collagen Ⅳ, which is probably correlated with its effects in alleviating the degree of brain edema.