Metastin和基质金属蛋白酶-9在裸鼠子宫内膜异位症模型中的表达及意义

Expression and Significance of Metastin and MMP-9 in the Nude Mice Endometriosis Model

目的:通过建立裸鼠子宫内膜异位症模型,探讨Metastin和基质金属蛋白酶-9(MMP-9)在不同生长阶段的异位内膜组织中的表达及两者之间的相互作用。方法:将生育年龄妇女的分泌晚期子宫内膜组织种植入裸鼠的盆腹腔,建立裸鼠子宫内膜异位症(EMs)模型,分别于5d、10d、15d、30d随机处死裸鼠,取异位生长的内膜组织作为研究组,以非EMs生育年龄妇女的子宫内膜组织作为对照组。采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法(SP法),检测不同生长阶段异位内膜中Metastin及MMP-9mRNA和蛋白的表达特性。结果:Metastin基因在5d、10d和15d组与对照组比较,表达降低,差异显著(P<0．05);30d组与对照组比较,无显著差异(P>0．05)。MMP-9基因在5d、10d、15d和30d组的表达与对照组比较,表达增强,差异显著(P<0．05);且15d组表达最强,与5d、10d、30d组比较差异显著(P<0．05)。Metastin和MMP-9两者mRNA表达比较成负相关(r=-0．575,P<0．01)。Metastin蛋白在进展期病灶组(5d、10d和15d)和晚期病灶(30d组)表达率分别为29．2%和75．0％,低于对照组人正常子宫内膜的表达率(100％);MMP-9蛋白在进展期病灶组(5d、10d和15d)和晚期病灶(30d组)表达率分别为87．5％和75．0％,高于对照组人正常子宫内膜的表达率(30．O％)。结论:Metastin表达减弱和MMP-9表达增强可能与内异症的侵袭过程有关,两者在。EMs发生发展中发挥重要作用。

Objective： To explore the gene and protein lesions acquired from nude mice killed at different times, expression of Metastin and MMP-9 in the endometriotie and the interaction between them. Methods： Normal human late secretory endometrium was put into abdominal cavity of nude nice to establish nude mice endometriosis model. Nude mice were killed at 5 d, 10 d, 15 d and 30 d, respectively, the ectopic growth endometrium （was obtained） as experiment group. The normal human late secretory endometrium was as control. Reverse transcript polymerase chain reaction （RT-PCR） and immunohistochemistry methods were utilized to examine the mRNA and protein expression of Metastin and MMP-9. Results： 5 d, 10 d and 15 d groups expressed lower level of Metastin than control group（P〈0.05）; and 30 d group had no difference with control group （P〉0.05）. However,5 d,10 d,15 d and 30 d groups expressed higher level of MMP-9 than control group （P〈0.05）; 15 d group expressed highest among all the groups （P〈0.05）. In addition, the negative correlation was observed between Metastin mRNA and MMP-9 mRNA （r=-0.575, P〈0.01）. The positive rates of meatstin protein in progressive phase group （5 d, l0 d and 15 d） and late phase group （30 d） were 29.2% and 75%, which were lower than control group （100%）（P〈0.05）. The positive rates of MMP-9 protein in progressive phase group and late phase group were 87.5% and 75%, which were higher than control group （30%）. Conclusion： The decreased expression of Metastin and the increased expression of MMP-9 may be involved in the invasion of endometriosis and they may play an important role in the genesis and development of endometriosis.