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目的分析基质金属蛋白酶(MMPs)及其抑制物(TIMPs)的mRNA在脑组织的表达,探讨血-脑脊液屏障(BBB)损伤致脑白质疏松症(LA)发生的作用机制。方法 18只5月龄雄性自发性高血压(SH)大鼠为实验组,同龄7只雄性Wistar大鼠为对照组。取大鼠脑组织,应用HE染色及免疫组织化学染色,观察其病理变化及髓鞘碱性蛋白(MBP)、神经中丝(NF)和胶质纤维酸性蛋白(GFAP)的表达。取大鼠脑白质组织,使用Real-time PCR技术,检测MMP-9、MMP-2和金属蛋白酶组织抑制物-1(TIMP-1)mRNA的表达水平。结果 HE染色显示,SH大鼠脑白质区神经元和少突胶质细胞数量减少,星形胶质细胞反应性增生。实验组较对照组GFAP表达增加,而MBP和NF表达减少。实验组大鼠脑白质区TIMP-1、MMP-9和MMP-2 mRNA表达水平升高。其中,TIMP-1与MMP-2 mRNA升高显著(P<0.05),而MMP-9 mRNA表达两组无显著性差异(P>0.05)。结论 5月龄SH大鼠可作为脑白质疏松症的实验动物模型。MMPs导致的BBB破坏可能是脑白质疏松症的发病机制之一。
Objective To analyze the expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in brain tissue and explore the mechanism of the pathogenesis of cerebral leukoaraiosis (LA) induced by blood-brain barrier (BBB) injury. Methods Eighteen male 5-month-old spontaneously hypertensive rats were used as the experimental group and 7 male Wistar rats of the same age as the control group. The brain tissue of rats was taken out. HE staining and immunohistochemical staining were used to observe the pathological changes and the expression of MBP, GFR and GFAP. The white matter of rat brain was extracted and the mRNA expression of MMP-9, MMP-2 and TIMP-1 were detected by Real-time PCR. Results HE staining showed that the number of neurons and oligodendrocytes in the white matter of the SH rats decreased and the astrocytes responded to hyperplasia. Compared with the control group, the GFAP expression increased and the expression of MBP and NF decreased in the experimental group. The expression of TIMP-1, MMP-9 and MMP-2 mRNA in the white matter of experimental rats increased. Among them, TIMP-1 and MMP-2 mRNA increased significantly (P <0.05), while MMP-9 mRNA expression had no significant difference between the two groups (P> 0.05). Conclusion 5-month-old SH rats can be used as experimental animal models of leukoaraiosis. BBB destruction caused by MMPs may be one of the pathogenesis of leukoaraiosis.