银杏内酯B对新生大鼠缺血性损伤海马MMP-2及MMP-9表达的影响

目的:观察银杏内酯B(GB)对缺氧缺血性脑损伤(HIBD)新生大鼠海马内基质金属蛋白酶MMP-2及MMP-9的影响,探讨GB的脑保护作用机制。方法:192只新生7天SD大鼠随机分为正常组(N组)、假手术组(S组)、HIBD模型生理盐水组(H组)和银杏内酯B治疗组(G组)。选择模型成功后24 h、4 d、10 d三个时间点,应用免疫组化、RT-PCR法检测各组大鼠海马CA1区MMP-2、MMP-9蛋白及mRNA的表达变化。结果:HIBD后海马MMP-2蛋白表达明显升高,4 d达高峰,10 d后开始下降;同时MMP-9蛋白表达也明显升高,但表达高峰在HIBD后24 h,4 d后开始下降。mRNA的表达趋势与蛋白表达相一致。N组可见极少量阳性表达细胞,S组中可见少量阳性表达细胞,G组的大鼠海马CA1区MMP-2、MMP-9的表达也明显升高,但是小于H组,G组的MMP-2、MMP-9的表达与H组相比差异有显著性(P<0.05)。结论:HIBD可引起MMP-2、MMP-9表达异常,并且呈动态变化;GB对脑保护作用机制之一可能与其抑制MMP-2、MMP-9高表达有关。

Influeace of GinkgolideB on marix metalloproteinase-2 and marix metalloproteinase-9 expressionin in hippocampus of rats with ischemic brain damage

Objective: To investigate effect of GinkgolideB on the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in rats ' hippocampus after hypoxic ischemic brain damage for the purpose to look into the brain protecting mechanism of GB.Methods: Seven-day-old SD rats(n=192) were randomly divided into four groups:Normal group、Sham group、HIBD group and GB treatment group.Immunohistochemistry and RT-PCR methods were used to detect MMP-2 and MMP-9 protein and mRNA expression changs in the hippocampus after obtaining successful animal model at three time points,i.e.the 24th hour,4th day and 10th day.Results: MMP-2 protein expression could be found to increase significantly,and reached the peak at the 4th day following HIBD,dropped later at the 10th day;There was significantly elevated MMP-9 protein expression,which reached the peak at the 24th hour following HIBD,deeveased later at the 3th day.Both MMP-2 and MMP-9 mRNA expression were observed in consistent with the protein expression.Almost no positive cells in the N group was found,while a few positive cells were found in the S group.Both MMP-2 and MMP-9 expression elevated obviously in the G group,but lower than those in the H group.There was significant difference in the MMP-2 and MMP-9 expression between the G group and the H group.Conclusions: Hypoxic ischemic brain damage might lead to unusual MMP-2 and MMP-9 expression and dynamic changes.Inhibition of MMP-2 and MMP-9 expression might be one protecting mechanism of ginkgolide B on hypoxic ischemic brain damage.