骨髓间充质干细胞来源的Exosome修复兔受损子宫内膜的研究

Bone marrow mesenchymal stem cell-derived Exosome repair damaged rabbit endometrium

目的:探讨骨髓间充质干细胞(BMSCs)来源的外泌体(Exo)对子宫内膜损伤修复的作用及机制。方法:将45只雌兔随机分为对照组、模型组和Exo治疗组,每组15只。机械和感染双重损伤法刮宫后,宫腔留置脂多糖棉线2d损伤子宫内膜,对照组只开腹不损伤。建模1周后,Exo治疗组于子宫肌壁间注射Exo悬液,其余两组等量注射PBS,分别于治疗后1、2、4周收集子宫组织。行HE和Masson染色,计算子宫内膜的腺体数量和纤维化面积,免疫组化法检测细胞角蛋白19(CK-19)、波形蛋白(VIM)表达。结果:治疗后4周,Exo组兔子宫内膜腺体数(26.17±1.254)显著高于模型组(10.92±0.848)(P<0.05),纤维化面积比率(19.52±0.539)显著低于模型组(49.25±1.239)(P<0.05),CK-19蛋白相对表达量显著高于模型组(P<0.05),VIM蛋白相对表达量显著低于模型组(P<0.05);Exo组各指标与对照组相比均无显著差异(P>0.05)。结论:BMSCs来源的Exo可促进受损子宫内膜腺体增生,抑制纤维化发展,促进子宫内膜修复。

Objective：To investigate the effect and mechanism of Exosome（Exo） derived from bone marrow mesenchymal stem cells（ BMSCs） on endometrium injury repairmen.Methods：A total of 45 female rabbits were randomly diveded into control group（ n = 15）,modeling group（ n = 15） and Exo treatment group（ n = 15）. After mechanical and infectious double injuries,retention of lipopolysaccharide cotton threads for 2 d were implemented to cause endometrium injury before uterine curettage.Only laparotomy was applied to control group instead of injuries.Exo suspension was injected to uterine intramural spaces 1 week after model establishment,PBS of the same volume was injected to the other two groups. Uterine tisues 1 w,2 w and4 w after treatment were respectively collected for HE and Masson staining in order to calculate the gland numbers and fibrosis area of endometrium.Immunohistochemical（ IHC） staining were adopted for the detection of Cytokeratin-19（ CK-19） and Vimentin（ Vim） expressions. Results：After 4 w of treatment,the gland number of Exo group（ 26. 17 ± 1. 254） was higher than that of modeling group（10.92±0.848）（ P〈0.05）,which the fibrosis area of Exo group was lower than modeling group（49.25±1.239） with statistical significance（ P〈0.05）. The expression of CK-19 protein was significantly higher than that in the modeling group（ P〈0. 05）,the expression of VIM protein was significantly lower than that in the modeling group（ P〈0.05） and no significant difference was discovered in each index compared with the control group（ P〉0.05）.Conclusion：Exo derived from BMSCs is able to promote gland hyperplasia in injured endometrium,to inhibit the development of fibrosis,and to improve the endometrium repairment.