褪黑素对脑出血大鼠基质金属蛋白酶表达及神经功能的影响

Effect of melatonin on MMP expression and neurological function in rats following intracerebral hemorrhage

目的观察褪黑素对脑出血大鼠神经功能缺损及血肿周围组织基质金属蛋白酶(MMP)表达的影响。方法将SD雄性大鼠85只,随机分为正常组10只、假手术组25只、模型组25只、褪黑素组25只;后2组建立脑出血模型,后3组随机于12h、1、2、4和7d处理,每个时间点5只。修正神经功能缺损评分(NSS)对各组大鼠进行神经功能评估;透射电子显微镜观察出血侧皮质微血管形态;RT-PCR技术定量分析脑组织MMP-2、MMP-9mRNA表达。结果褪黑素组1~7dNSS低于模型组(P<0.05);褪黑素组和模型组12h^4dMMP-2mRNA水平均逐渐升高,褪黑素组7dMMP-2mRNA明显低于模型组(P<0.05);模型组MMP-9mRNA 2d显著升高,褪黑素组MMP-9mRNA峰值1d出现,7d再次升高,并明显高于模型组(P<0.05)。结论褪黑素能够改善脑出血大鼠神经功能,对脑出血具有保护作用,其机制可能与褪黑素通过调控MMP-2和MMP-9转录,减轻血管源性脑水肿相关。

Objective To observe the effect of melatonin （MT） on neurological function and MMP2/9 expression in rats following intracerebral hemorrhage （ICH） .Methods Eighty-five SD rats were randomly divided into normal group （n=10） ,sham operation group（n=25） ,ICH model group （n= 25） and MTintervention group （n= 25） .Rats in ICH model group ,sham operation group and MTintervention group were divided into 12h group ,1d group ,2d group ,4d group and 7d group （5 in each group） .Their neurological function was assessed according to the modified NSS .Morphology of microvascular structure was observed under electron microscope .Expression of MMP2/9 mRNA was detected by RT-PCR .Results The NSS score was significantly lower in MTintervention group than in model group on days 1-7 after ICH （P〈0 .05） .The expression level of MMP2 mRNA was significantly higher in MT intervention group than in model group from 12h to 4d after ICH and significantly lower on day 7 after ICH （P〈0 .05） .The expression level of MMP9 mRNA increased significantly in model group on day 2 after ICH and reached its peak in MT intervention group on day 1 after ICH .The expression level of MMP9 mRNA was significantly higher in MTintervention group than in model group on day 7 after ICH （P〈0 .05） .Conclusion MTimproves the neurological function in rats following ICH by regulating the MMP2/9 expression and alleviating the vasogenic brain edema .