RAP1A和EPAC1在卵巢子宫内膜异位症组织中的表达及意义

Expression and significance of RAP1A and EPAC1 in ovarian endometriosis

目的检测RAS相关蛋白1(RAP1)的异构体RAP1A和环磷酸腺苷交换蛋白1(EPAC1)在卵巢子宫内膜异位症的表达和分布,探讨两者在疾病发生、发展中的作用及意义。方法收集2019年6月—2020年1月在中南大学湘雅医院妇科行腹腔镜下卵巢子宫内膜异位症手术患者的临床资料及组织,采用免疫组织化学法检测RAP1A和EPAC1在异位内膜、在位内膜、正常内膜的表达和分布情况,采用Western blotting法检测蛋白的表达,分析RAP1A和EPAC1表达的相关性。结果RAP1A表达于腺上皮细胞及间质细胞的细胞质,在在位内膜腺上皮细胞呈强阳性表达;EPAC1表达于腺上皮细胞的细胞质,在间质细胞的细胞质和细胞核都有表达,在腺上皮细胞的细胞质呈强阳性表达。2种蛋白在异位内膜、在位内膜及正常内膜的表达比较,差异有统计学意义(P<0.05),其中异位内膜、在位内膜的表达均高于正常内膜(P<0.05),异位内膜与在位内膜的表达差异无统计学意义(P>0.05)。Pearson相关性分析显示,RAP1A和EPAC1的表达水平在异位内膜(r=0.635,P<0.05)、在位内膜(r=0.697,P<0.05)和正常子宫内膜(r=0.436,P<0.05)均呈正相关。结论RAP1A和EPAC1在卵巢子宫内膜异位症中呈高表达,两者可能相互协同,促进异位病灶的发生、发展。

Objective To detect the expression and distribution of Ras-associated protein 1A(RAP1A)and the exchange protein directly activated by cAMP1(EPAC1)in ovarian endometriosis,and to explore their clinical significance in development of the disease.Methods The clinical data and tissues of patients with ovarian endometriosis who underwent laparoscopic surgery in Xiangya Hospital of Central South University from June 2019 to January 2020 were collected.Immunohistochemistry was used to detect the location of RAP1A and EPAC1 proteins in ectopic endometrium,eutopic endometrium and normal endometrium;while Western blot was done to measure the expression of the two proteins.Then,the correlation between RAP1A and EPAC1 expression was analyzed.Results RAP1A protein was located in cytoplasm,and was significantly higher in ectopic endometrium and eutopic endometrium of ovarian endometriosis than that in normal endometrium,and strongly positive in glandular epithelial cells of eutopic endometrium.EPAC1 protein was located in not only cytoplasm of glandular epithelial cells,but in both cytoplasm and nucleus of stromal cells;its expression in endometriosis was significantly higher than that in normal endometrium,and especially strongly ectopic endometrium and eutopic endometrium of ovarian positive in the cytoplasm of glandular epithelial cells.The expressions of RAP1A and EPAC1 had significant differences among 3 groups.The both expressions in ectopic endometrium and eutopic endometrium were higher than those in normal endometrium.The expressions of RAP1A and EPAC1 in ectopic endometrium,eutopic endometrium and normal endometrium of ovarian endometriosis were positively correlated,and the correlation coefficients were 0.635,0.697 and 0.436,respectively(all P<0.05).Conclusions RAP1A and EPAC1 are highly expressed in ovarian endometriosis,and they could be cooperated with each other to facilitate the development of ectopic lesions.