MMP-2、TIMP-2在内毒素诱导性葡萄膜炎中的表达

Expression of MMP-2 and TIMP-2 in Endotoxin-induced Uveitis

目的 探讨基质金属蛋白酶 2 (MMP 2 )及其组织型抑制剂 (TIMP 2 )在内毒素诱导性葡萄膜炎 (EIU)模型中的表达及意义。方法 2 0 0 μg伤寒杆菌内毒素注射于SD大鼠双后足垫 ,建立EIU模型。用免疫组织化学方法检测MMP 2、TIMP 2在内毒素注射后不同时间点 (0、 6、 12、 18、 2 4、 4 8、 72、 96h和 7d)的表达。结果 内毒素注射后 6h开始出现炎症 ,于 2 4h炎症达到高峰 ,以后逐渐减轻 ,7d时基本消退。虹膜、睫状体的上皮细胞和渗出的炎性细胞表达MMP 2和TIMP 2。MMP 2在 6h表达开始增高 ,18～ 2 4h达高峰 ,以后逐渐下降。TIMP 2于 12h出现表达 ,4 8h达高峰 ,以后逐渐下降。TIMP 2和MMP 2平均吸光度值的比值与炎症程度呈负相关。结论 MMP 2是与炎症反应相关的调节因子 ,其过量表达参与葡萄膜炎的发病。减低MMP 2的活性或降低MMP 2 /TIMP 2的比值可能为治疗葡萄膜炎的新思路。

Objective To study the expression of matrix metalloproteinase- 2 (MMP-2) and its tissue inhibitor (TIMP-2) in the uvea in the model of endoto xin induced uveitis(EIU).Methods EIU model was established by injecting a dose of 200 μ g endotoxin (Salmonella typhimurium Lipopolysaccharide, LPS) into the footpa ds of SD rats. The uvea was obtained from control animals and those with EIU at 0, 6, 12, 18, 24, 48, 72, 96 h and 7 days after LPS injection. The expression of MMP-2 and TIMP-2 was detected by immunohistochemistry, and the results (A ) were analyzed by computer medical image analysis system. Results Intraocular inflammation appeared at 6 h after LPS inje ction, peaked at 24 h, and eliminated at 7 day. The expression of MMP-2 and TIM P-2 was detected in the epithelial cells of ciliary body, iris and exudated inf lammatory cells. The expression of MMP-2 was elevated at 6 h, peaked at 18—24 h and dropped gradually afterwards. The expression of TIMP-2 was detected at 12 h, reached peaks at 48 h, and decreased gradually. There was a negative correla tion between the A values of TIMP-2/ MMP-2 and the severity of uveitis. Conclusion MMP-2 and TIMP-2 may be important mediators of the inflammatory response and contribute to matrix remodeling observed in uveitis a nd may take part in the mechanism of uveitis. Therapeutic strategies aimed at re ducing MMP activity and decreasing the value of MMP-2/TIMP-2 may be of some be nefit in the treatment of uveitis.