基质金属蛋白酶9在实验性自身免疫性脑脊髓炎大鼠发病过程中的动态表达

目的通过检测基质金属蛋白酶-9(MMP-9)在EAE大鼠发病过程中不同阶段外周血和中枢神经系统中的表达水平及动态变化,以探讨其在多发性硬化发病过程中的作用及机制。方法 Wistar雌性大鼠80只,分为模型组(EAE组)、完全福氏佐剂组(CFA组),分别于免疫后6天、8天、10天、12天、14天、16天、18天及20天取视交叉处脑组织和脊髓腰膨大段行HE染色观察炎性细胞的浸润状况;免疫组化法检测脑和脊髓组织中MMP-9的表达,酶联免疫吸附实验测定血清中MMP-9的含量。结果 EAE组大鼠脊髓和脑组织中MMP-9阳性细胞数及血清中MMP-9水平均显著高于同期CFA组(P<0.05);EAE 10天组与EAE 6天、14天、18天及20天组比较,大鼠脊髓腰膨大处MMP-9阳性细胞数较多(P<0.05);EAE 12天组与EAE 6天组、8天组、14天组、16天组、18天组及20天组比较,大鼠脑组织视交叉处MMP-9阳性细胞数较多(P<0.05);EAE 12天组与EAE 6天组、8天组、10天组、14天组、16天组、18天组及20天组相比较,大鼠血清中MMP-9含量较高(P<0.05)。结论在EAE大鼠发病前期即有中枢组织内MMP-9的高表达,且EAE大鼠脊髓中MMP-9的高表达要早于脑组织和外周血,但MMP-9表达的高峰在第12天与病理变化和疾病进展是同步的。

The dynamic expression of MMP-9 in different course of experimental autoimmune encephalomyelitis rats

Objective To establish a rat model of autoimmune encephalomyelitis, and detect the expression of the MMP-9 levels in the peripheral blood and the central nervous system , observe the changes of pathogenesis in EAE. Methods 80 female Wistar rats, were randomly divided into EAE group , and CFA group. The rats were sacrificed at different time after immunized： 6,8,10, 12, 14, 16 天, 18,20 day. Observing the infiltration of inflammatory cells by HE staining, and evaluating the express level of MMP-9 in brain tissue and spinal cord by immunohistochemical staining. Assessing the serum level of MMP-9 by enzyme-linked immunosorbent. Results Compared with the CFA group, the MMP-9 positive cells in the spinal cord, the brain tissue and the serum of the EAE group was statistically significant （P 〈0.05）. Compared with the 6-day group, 14-day group, 18-day group, 20-day group, the MMP-9 positive cells in the spinal cord lumbar enlargement of the 10-day group was statistically significant （P 〈0.05）. Compared with the 6-day group, 8-day group, 14-day group, 16-day group, 18-day group, 20-day group, the MMP-9 positive cells in the brain tissue at the optic chiasm of the 10-day group was statistically significant （P 〈 0.05）. Compared with the 6-day group, 8-day group, 10-day group, 14-day group, 16-day group, 18-day group, 20-day group of the EAE group, the 12-day group of the EAE had a the higher serum MMP-9 level, and which is statistically significant （P 〈 0.05 ）. Conclusion There is a high expression of MMP-9 in central nervous system at the early onset of EAE rat, And the high expression of MMP-9 in spinal cord is earlier than in the brain and serum. MMP-9 expression peak is in the 12th day. and the expression were in coincident with the pathological changes and disease progression.