【摘要】 目的：为研究外伤性PVR和外伤后应用GM6001干预大鼠视网膜组织MMP9及TIMP1、在不同病程中的表达变化。
方法：360只SD大鼠随机分为正常对照组、外伤性PVR组和外伤后应用GM6001组。正常对照组玻璃体腔内注射生理盐水；外伤性PVR组玻璃体腔内注射PRP血浆制成外伤性PVR大鼠动物模型；外伤后应用GM6001组在外伤后12h玻璃体腔内注射GM6001。应用免疫组化染色方法分别于1，3，7，14，21，28d对各组大鼠视网膜组织MMP9及TIMP1的表达检测。
结果：免疫组化结果示MMP9、TIMP1蛋白均主要表达于视锥视杆层、视网膜内外网状层、神经纤维层。MMP9在正常对照组、外伤后应用GM6001组的各个亚组微弱表达。MMP9在外伤性PVR组1，3，7d显著表达，与正常对照组和外伤后应用GM6001组的差异有显著性 (P﹤0.01)，随着病程的延长，MMP9的表达呈进行性减弱的趋势； TIMP1在外伤性PVR组与外伤后应用GM6001组的各个亚组均有明显表达，与正常对照组的差异均有显著性 (P﹤0.01)。MMP9／TIMP1比率在外伤性PVR组1，3，7d增高, 与正常对照组和外伤后应用GM6001组的差异均有显著性 (P﹤0.05)。
结论：MMP9、TIMP1参与了PVR发生发展的病理过程，MMP9/TIMP1比率增高促进PVR发生发展的进程。人工合成基质金属蛋白酶抑制剂GM6001可促进MMP9/TIMP1动态平衡的重新建立，从而在外伤性PVR的防治中起重要作用。
【关键词】 基质金属蛋白酶9 基质金属蛋白酶抑制剂 1 GM6001 外伤性增生性玻璃体视网膜病变 免疫组化
Expression of MMP9,TIMP1 on the traumatic PVR retina of SD rats
GuoXing Xu, ChunYan Feng
Foundation item: National Natural Foundation of Fujian Province (No.C0510015)
Department of Ophthalmology, the First Affiliated Hospital of Fujian Medical University; Fujian Institute of Ophthalmology, Fuzhou 350005, Fujian Province, China
Abstract
AIM: To investigate the expression of MMP9 and TIMP1 during the course of traumatic PVR treated with GM6001 and without GM6001, to explore the potential role of MMP9 and TIMP1 during the course of traumatic PVR and to evaluate the effect of GM6001 on traumatic PVR prevention and treatment.
METHODS: Totally 360 SD rats were divided randomly into three groups: normal control group, the traumatic PVR group, the traumatic PVR treated with GM6001 group. The normal control group was intravitreous injected with normal saline. The traumatic PVR group was intravitreous injected with the PRP. The traumatic PVR treated with GM6001 group was intravitreous injected with the PRP and GM6001. The expression of MMP9 and TIMP1 were qualitative and semiquantitative analyzed with immunohistochemistry on day 1, 3, 7, 14, 21 and 28.
RESULTS: Immunohistochemistry showed that the expression of MMP9 and TIMP1 were mainly located in the photoreceptor cells layer, out plexiform layer, inner plexiform layer and nerve fiber layer. The expression of MMP9 in the normal group and the traumatic PVR treated with GM6001 group were weak at all time. The expression of MMP9 in the traumatic PVR group was strong at day 1, 3 and 7. The differences were statistically significant as compared with the normal group and the traumatic PVR treated with GM6001 group (P<0.01). The expression of MMP9 in the traumatic PVR group decreased at the following time. The expression of TIMP1 in the traumatic PVR group and the traumatic PVR treated with GM6001 group were strong at all time. The differences were statistically significant as compared with the normal group (P<0.01). The rate of MMP9／TIMP1 in the traumatic PVR group increased at day 1, 3 and 7. The differences were statistically significant as compared with the normal group and the traumatic PVR treated with GM6001 group (P<0.05).
CONCLUSION: MMP9 and TIMP1 involve in the course of traumatic PVR. The higher rate of MMP9／TIMP1 promotes the course of traumatic PVR. GM6001 plays an important role in the course of traumatic PVR prevention and treatment by regulating the rate of MMP9／TIMP1.
KEYWORDS: matrix metalloproteinase9; tissue inhibitors of metalloproteinase1; GM6001; traumatic proliferative vitreoretinopathy; immunohistochemistry
0引言
增生性玻璃体视网膜病变（proliferative vitreoretinopathy,PVR）属于眼内组织创伤愈合过度修复的病理过程，细胞外基质（extracellular matrix,ECM）与基底膜的降解、合成及重塑贯穿于这一复杂的损伤与修复的全过程。ECM是填充于细胞间的物质，其成分除水、电解质、少量液相成分之外，主要还有胶原、粘连糖蛋白、蛋白多糖，共同构成了细胞生长的微环境。不仅是细胞的支架结构,在维持正常组织结构和功能、细胞生长和分化、炎症反应和伤口愈合等过程中占有非常重要的地位,而且能调控细胞迁移、增殖、粘附和基因表达。本研究基质金属蛋白酶9（matrixmetall oproteinase9,MMP9)以及抑制剂基质蛋白酶组织抑制物1（tisse inhibitor of metalloproteinase1,TIMP1）在正常眼球和外伤性PVR眼球及外伤后应用GM6001治疗眼球中的表达变化，探讨人工合成基质金属蛋白酶抑制剂预防和治疗外伤性PVR的可能机制，为临床应用人工合成基质金属蛋白酶抑制剂预防和治疗外伤性PVR提供实验基础。
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