人脐带间充质干细胞对卵巢早衰大鼠模型的潜在治疗机制  

Potential Therapeutic Mechanisms of Human Umbilical Cord Mesenchymal Stem Cells in Rat Model of Premature Ovarian Failure

作　　者：杨宏 代文杰 杜星 付旭锋 YANG Hong;DAI Wenjie;DU Xing;FU Xufeng(Key Laboratory of Fertility Preservation and Maintenance,Ministry of Education,Ningxia Medical University,Yinchuan 750004,China;School of Basic Medical Science,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学生育力保持教育部重点实验室,银川750004 [2]宁夏医科大学基础医学院,银川750004

出　　处：《宁夏医科大学学报》2023年第12期1214-1221,共8页Journal of Ningxia Medical University

基　　金：国家自然科学基金项目(81960270)。

摘　　要：目的探讨人脐带间充质干细胞(hUC-MSCs)对卵巢早衰(POF)的治疗作用及其机制。方法将22只清洁级雌性SD大鼠接受环磷酰胺腹腔注射,连续注射14 d,构建POF模型,POF大鼠模型建立成功后,对其中11只POF大鼠注射生理盐水作为对照组(POF组),其余11只通过尾静脉移植培养状态良好的hUC-MSCs(POF+MSCs组),分别在第2天、第10天和第18天安乐处死两组大鼠并进行心脏采血,最后收集血清进行蛋白芯片检测和生物信息学分析。结果与POF组相比,hUC-MSCs治疗后第2天,促炎因子白细胞介素(IL)-2、IL-6和IL-2Rα表达均上调(P均<0.05);治疗后第10天,促炎因子IL-2Rα表达下调(P<0.05);治疗后第18天,促炎因子肿瘤坏死因子-α(TNF-α)和IL-1β表达均下调(P均<0.05)。与hUC-MSCs治疗后第2天相比,hUC-MSCs治疗后第18天,促炎因子γ干扰素(IFNG)、TNF-α和IL-1β表达均下调(P均<0.05),并且在GO富集分析的生物学过程中涉及调控炎症相关通路的变化;在KEGG富集分析的结果中,与炎症相关的主要信号通路JAK-STAT也有显著富集,提示hUC-MSCs在体内可能通过JAK-STAT信号通路来抑制促炎因子,从而改善炎性反应。结论hUC-MSCs进入体内后可能通过JAK-STAT信号通路改善炎性反应,进而改善POF的卵巢功能。Objective To investigate the therapeutic effect and mechanism of human umbilical cord mesenchymal stem cells(hUC-MSCs)on premature ovarian failure(POF).Methods Twenty-two female Sprague-Dawley(SD)rats were intraperitoneally injected with cyclophosphamide for 14 days to establish the POF model.After the POF model was successfully established,11 POF rats were injected with normal saline as the control group(POF group),and the other 11 rats were transplanted with hUC-MSCs in good culture condition(POF+MSCs group)through the tail vein.Then the rats in the two groups were sacrificed on the 2 nd,10 th and 18 th day,respectively,and blood samples were collected from the heart.Finally,serum samples were collected for protein chip detection and bioinformatics analysis.Results Compared with the POF group,on the second day after the treatment of hUC-MSCs group,the expression of inflammation factors IL-2,IL-6,and IL-2Rαwas raised(P all<0.05).On the 10 th day after treatment,pro-inflammatory factor IL-2Rαexpression decreased(P<0.05).On the 18 th day after treatment,the inflammatory factors TNF-αand IL-1βexpression were lowered(P all<0.05).Compared with hUC-MSCs treatment for 2 days,the expression of inflammation factor IFNG,TNF-αand IL-1βdecreased(P all<0.05),and the GO rich analysis of the biology process involved changes in regulating inflammation-related pathways on the 18 th day after hUC-MSCs treatment.In the results of KEGG enrichment analysis,the related signal pathway JAK-STAT was also significantly enriched,suggesting that hUC-MSCs may suppress inflammatory factors through the JAK-STAT signaling pathway in the body,thereby improving the inflammatory response.Conclusion hUC-MSCs may improve the ovarian function of POF by regulating inflammatory response through JAK-STAT signaling pathway.

关 键 词：人脐带间充质干细胞 卵巢早衰 蛋白芯片 炎性反应 

分 类 号：R394.1[医药卫生—医学遗传学]