孕酮对新生大鼠低氧缺血性脑损伤中MMP-3表达的影响

目的：研究孕酮（PROG）对新生大鼠低氧缺血后脑内基质金属蛋白酶3（MMP-3）表达的影响。方法：建立新生大鼠低氧缺血性脑损伤动物模型,伊文思兰（EB）染色和电镜观察新生鼠低氧缺血性脑损伤血一脑屏障的通透性改变;免疫印迹（Western blot）方法检测大脑皮层MMP-3表达。结果：电镜显示低氧缺血组血-脑屏障完整性明显破坏：EB染色结果表明低氧缺血组血-脑屏障通透性明显高于假手术组,差异极显著（P〈0．01）,孕酮组血-脑屏障通透性明显低于低氧缺血组,有显著性差异（P〈0．05）;Western blot结果显示低氧缺血组MMP-3蛋白表达显著高于假手术组（P〈0．01）;孕酮组MMP-3蛋白表达显著低于低氧缺血组（P〈0．05）。结论：孕酮通过减少MMP-3的表达,降低血一脑屏障的损伤,这可能是其发挥脑保护作用的机制之一。

Effect of progesterone on MMP-3 expression in neonatal rat brain after hypoxic-ischemia

Objective： To starty the effect of progesterone on matrix metalloproteinase-3 （MMP-3） expression in neonatal rat brain after hypoxie-ischemia. Methods： Followed the hypoxic-lschemia of neonatal rat brain, Evans blue（EB） staining and transmission electron mi- croscopy were used to detect the blood-brain barrier pathological changes on permeability. MMP-3 protein expression in cerebral cortex was measured with Western blot, Results： Transmission electron microscopy results showed that the blood brain barrier in hypoxic-ischemic group changed significantly compare to progesterone group. EB staining results suggested that the blood-brain barrier permeability of hypoxic-ischemic group was significantly increased compared to sham-operated group（ P 〈 0.01 ）. The blood-brain barrier permeability in progesterone group was also decreased in comparison to that of hypoxic-isohemie group （P 〈 0.05）. Western blot image analysis results indicated that MMP-3 protein expression in the hypexic-ischemic group increased significantly than that in sham-operated group（ P 〈 0.01 ）, and the progesterone group was decreased significantly than that in hypoxic-ischemic group （ P 〈 0.05）. Conclusion： Progesterone may reduce the blood-brain barrier damage by reducing MMP-3 expression. This might be one of the protective mechanisms in the hypoxic-ischemie brain injury.