基质金属蛋白酶及其抑制剂对外伤性PVR的影响研究

发布时间：2018-01-26 15:52

本文关键词：基质金属蛋白酶-2 基质金属蛋白酶-9 基质金属蛋白酶抑制剂-1 基质金属蛋白酶抑制剂-2 GM6001 外伤性增生性玻璃体视网膜病变免疫组化逆转录聚合酶链反应　出处：《福建医科大学》2007年硕士论文　论文类型：学位论文

【摘要】： 目的:观察外伤性PVR和外伤后应用GM6001大鼠视网膜组织MMP-2、MMP-9及TIMP-1、TIMP-2在不同病程中的表达变化,以期探讨MMP-2、MMP-9及TIMP-1、TIMP-2在PVR形成过程中的作用,评价GM6001防治外伤性PVR的效果。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和逆转录聚合酶链反应(RT-PCR)法分别于1、3、7、14、21、28d对各组大鼠视网膜组织MMP-2、MMP-9及TIMP-1、TIMP-2的表达进行定性、定位、半定量检测。结果: 1、免疫组化结果示MMP-2、MMP-9、TIMP-1、TIMP-2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。 2、MMP-2、MMP-9在正常对照组、外伤后应用GM6001组的各个亚组微弱表达。MMP-9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㩳0.01),随着病程的延长,MMP-9的表达呈进行性减弱的趋势;MMP-2在外伤性PVR组142128d表达增强,与正常对照组和外伤后应用GM6001组的差异有显著性(P㩳0.01),随着病程的延长,MMP-2的表达呈进行性增高的趋势。TIMP-1、TIMP-2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㩳0.01)。 3、MMP-9/TIMP-1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组的差异有显著性(均P㩳0.05);MMP-2/TIMP-2比率外伤性PVR组142128d增高,与正常对照组和外伤后应用GM6001组的差异有显著性(均P㩳0.05)。 4、RT-PCR结果示MMP-2、MMP-9、TIMP-1、TIMP-2mRNA以及MMP-2/TIMP-2和MMP-9/TIMP-1的比率与免疫组织化学结果相平行。结论: MMP-2、MMP-9、TIMP-2、TIMP-1参与了PVR发生发展的病理过程,MMP-2"TIMP-2、MMP-9"TIMP-1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MMP-2"TIMP-2、MMP-9"TIMP-1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。
[Abstract]:Objective: to observe the changes of MMP-2MMP-9 and TIMP-1 TIMP-2 expression in retina of traumatic PVR and post-traumatic GM6001 rats. The purpose of this study was to investigate the role of MMP-2, MMP-9 and TIMP-1 and TIMP-2 in the formation of PVR, and to evaluate the effect of GM6001 on the prevention and treatment of traumatic PVR. Methods Twenty six hundred and thirty six Sprague-Dawley rats were randomly divided into three groups: normal control group, traumatic PVR group and post-traumatic GM6001 group. Traumatic PVR rat model was established by intravitreal injection of PRP plasma into the vitreous cavity of traumatic PVR group. GM6001 was injected into the vitreous cavity 12 hours after injury in GM6001 group. Immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR) were used to detect GM6001. The expression of MMP-2MMP-9 and TIMP-1 TIMP-2 in the retina of rats in each group were detected qualitatively, locally and semi-quantitatively. Results: 1. The results of immunohistochemistry showed that MMP-2, MMP-9, TIMP-1and TIMP-2 were mainly expressed in the optic cone layer, the inner and outer retina reticular layer, and the nerve fiber layer. (2) MMP-2MMP-9 was expressed weakly in the normal control group and each subgroup of the GM6001 group after trauma. MMP-9 was expressed in the traumatic PVR group 1? 3? After 7 days, there was a significant difference in the expression of GM6001 between the normal control group and the post-traumatic GM6001 group. The expression of MMP-9 was gradually decreased with the prolongation of the course of disease. The expression of MMP-2 in traumatic PVR group was 14? 21? After 28 days, the expression of GM6001 was significantly higher than that of normal control group and post-traumatic GM6001 group. The expression of MMP-2 increased gradually with the prolongation of the course of disease. The expression of TIMP-2 in all subgroups of traumatic PVR group and post-traumatic GM6001 group was significantly higher than that in normal control group. 0.01g. 3The ratio of MMP-9 / TIMP-1 in traumatic PVR group was 1? 3? After 7 days, there was a significant difference between normal control group and post-traumatic GM6001 group (P < 0.05). The ratio of 0. 05% MMP-2 / TIMP-2 in traumatic PVR group was 14? 21? After 28 days, there was a significant difference between normal control group and post-traumatic GM6001 group (P < 0.05). 0.05. 4 the results of RT-PCR showed that MMP-2, MMP-9 and TIMP-1. The ratios of TIMP-2mRNA, MMP-2/TIMP-2 and MMP-9/TIMP-1 were parallel to those of immunohistochemistry. Conclusion: MMP-2, MMP-9, TIMP-2 and TIMP-1 are involved in the pathogenesis and development of PVR with MMP-2 "TIMP-2." The increase of MMP-9 "TIMP-1 ratio promotes the development of PVR. Synthetic matrix metalloproteinase inhibitor GM6001 can promote MMP-2" TIMP-2. The establishment of dynamic balance of MMP-9 "TIMP-1" plays an important role in the prevention and treatment of traumatic PVR.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R779.1

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