GRIM-19在子宫腺肌病中的表达及促进疾病发展的机制研究

Expression of GRIM-19 in adenomyosis and its mechanism for promoting disease progress

目的研究诱导细胞凋亡相关基因-19(GRIM-19)在子宫腺肌病患者子宫内膜组织中的表达水平,并探讨其在疾病发生发展中的分子机制。方法取30例子宫腺肌病患者异位和在位内膜组织,采用免疫组织化学和Western blot检测内膜组织中GRIM-19、磷酸化信号转导及转录激活蛋白3(pSTAT3)和内皮生长因子(VEGF)的表达水平。采用TUNEL检测内膜组织凋亡,CD34抗体直接检测内膜组织新生血管形成。构建GRIM-19siRNA和重组质粒,转染Ishikawa细胞后检测下游信号分子pSTAT3、信号转导和转录激活因子3(STAT3)和VEGF的变化。结果与对照组相比,子宫腺肌病患者在位内膜和异位内膜组织中GRIM-19表达水平降低。在位内膜和异位内膜组织中细胞凋亡减少,微血管密度、pSTAT3和VEGF表达水平升高。转染Ishikawa细胞,下调GRIM-19表达可显著激活pSTAT3和VEGF。结论 GRIM-19通过抑制细胞凋亡和增加新生血管形成,促进子宫腺肌病的发生发展。

Objective To study the expression level of GRIM-19 in endometrial tissue of the patients with adenomyosls and to investigate its molecular mechanism during disease occurrence and progress process. Methods The ectopic and eutopic endometrial tissues were obtained from 30 patients with adenomyosis. Immunohistochemistry and Western blot were performed to detect the expression of GRIM-19, pSTAT3 and VEGF. The endometrial nssue apoptosis was assayed by TUNEL. Immunohistochemistry with anti-CD34 antibody was performed to detect angiogenesis in endometrial tissue. GRIM-19 small interfering RNA（siRNA） and recombinant GRIM-19 plasmid were constructed and transfected into Ishikawa cells for detecting the change of downstream signal molecules pSTAT3, STAT3 and VEGF. Results The expression level of GRIM-19 was decreased in the ectopic and eutopic endometrial tissues of patients with adenomyosis compared with control group. Apoptosis in ectopic and eutopic endometrial tissues was reduced;the mierovessel density and expression levels of pSTAT3 and VEGF were increased. Transfecting Ishikawa cells and downregulating GRIM-19 expression could significantly activate pSTAT3 and VEGF. Conclusion GRIM-19 promotes the occurrence and development of adenomyosis by inhibiting apoptosls and anglogenesis.