摘要
目的:近年来卵巢早衰发病率呈现上升和年轻化趋势,因卵巢早衰病因复杂且临床治疗效果不佳,亟需寻求一种安全有效的治疗方式。文章系统评价干细胞移植治疗卵巢早衰动物模型的有效性。方法:计算机检索PubMed、The Cochrane Library、EMbase、CBM、中国知网、万方和维普数据库,收集关于干细胞移植后对卵巢早衰动物模型修复的相关性文献,检索时间从各数据库建库至2020-06-10。由2位评价员独立筛选文献并提取数据,采用SYRCLE动物实验偏倚风险评估表进行文献质量评价。采用RevMan 5.3软件对结局指标进行Meta分析。结果:①共纳入13篇随机对照动物实验文献,文献总体为中等质量,共348只小鼠,干细胞组184只采用干细胞移植治疗,对照组164只采取空白对照、生理盐水或者PBS干预;②Meta分析结果显示:与对照组相比,干细胞组血清雌激素水平(SMD=3.02,95%CI:1.87-4.18,P<0.00001)、血清抗苗勒管激素水平(ng/mL亚组:SMD=4.77,95%CI:0.95-8.59,P=0.01;pg/mL亚组:SMD=4.94,95%CI:0.91-8.97,P=0.02)、血清黄体生成素水平(SMD=-1.47,95%CI:-1.73至-1.22,P<0.00001)、各级卵泡数目(SMD=1.91,95%CI:0.85-2.97,P=0.0004)和生育率均提高(RR=2.07,95%CI:1.39-3.09,P=0.0004),而血清卵泡刺激素水平降低(P<0.0001);干细胞治疗组各级卵泡数目明显高于对照组(P<0.05);亚组分析显示,随着随访时间的延长,原始卵泡、初级卵泡及次级卵泡数目显著提高(P<0.05),闭锁卵泡数目明显下降(P<0.05),不同干细胞类型移植均可改善血清雌激素水平,且随着注射干细胞单位剂量的增加血清雌激素水平恢复更加显著(P<0.05)。结论:现有的动物实验证据表明,干细胞移植治疗卵巢早衰模型小鼠疗效确切,干细胞移植后促使卵巢早衰模型小鼠血清雌激素水平升高,卵泡刺激素水平下降,各级卵泡数量得到明显改善,有助于卵巢功能恢复,但其临床应用效果未来仍需大样本、高质量的临床试验来验证。
OBJECTIVE:In recent years,the incidence of premature ovarian failure has been on the rise,showing the young trend.Because of the complex etiology of premature ovarian failure and poor clinical outcome,there is an urgent need to find a safe and effective treatment modality.This study systemically assessed the effectivity of stem cell transplantation of premature ovarian failure animal models.METHODS:PubMed,The Cochrane Library,EMbase,CBM,CNKI,Wanfang,and VIP were retrieved before June 10,2020.A series of studies on the treatment of premature ovarian failure animal models by stem cells were collected.Two evaluators independently screened the literature and extracted the data.The SYRCLE risk of bias assessment scale for animal experiments was used to evaluate the quality of the literature.The primary outcome indicators were analyzed using RevMan 5.3 software for meta-analysis.RESULTS:(1)A total of 13 randomized controlled animal experimental studies were included,with 348 mice,and overall quality was moderate.Stem cell group(n=184)only received stem cell transplantation,and control group(n=164)only received blank control,normal saline or PBS intervention.(2)Meta-analysis results showed that compared with the control group,serum estrogen level(SMD=3.02,95%CI:1.87-4.18,P<0.00001),serum anti-Müllerian hormone level(ng/mL subgroup:SMD=4.77,95%CI:0.95-8.59,P=0.01;pg/mL subgroup:SMD=4.94,95%CI:0.91-8.97,P=0.02),serum luteinizing hormone level(SMD=-1.47,95%CI:-1.73 to-1.22,P<0.00001),the number of follicles at all levels(SMD=1.91,95%CI:0.85-2.97,P=0.0004)and fertility rate increased(RR=2.07,95%CI:1.39-3.09,P=0.0004),but serum follicle-stimulating hormone level decreased(P<0.0001)in the stem cell group.The number of follicles at all levels was significantly higher in the stem cell group than that in the control group(P<0.05).Subgroup analysis showed that with the increase of follow-up time,the number of primordial follicles,primary follicles and secondary follicles was significantly increased(P<0.05),and the number of atresic follicles was significantly decreased(P<0.05).Different types of stem cell transplantation could improve the serum estrogen level,and the recovery of serum estrogen level was more significant with the increase of unit dose of stem cell injection(P<0.05).CONCLUSION:Available evidence from animal studies suggests that stem cell transplantation is effective in treating premature ovarian failure model mice.Stem cell transplantation induces an increase in estrogen levels,a decrease in follicle-stimulating hormone levels,and an improvement in follicle numbers at all levels in premature ovarian failure.Stem cells have some restorative effects on the ovary,but large samples and high quality human trials are still needed to verify clinical application effects.
作者
赵淑颖
郭广玲
刘晨晨
张超
董斯睿
龚琴琴
计璐伟
Zhao Shuying;Guo Guangling;Liu Chenchen;Zhang Chao;Dong Sirui;Gong Qinqin;Ji Luwei(Postgraduate Training Base,Taihe Hospital,Jinzhou Medical University,Shiyan 442000,Hubei Province,China;Taihe Hospital,China Anti-aging Center of Affiliated Hospital of Hubei University of Medicine,Shiyan 442000,Hubei Province,China;Center for Evidence-Based Medicine and Clinical Research,Affiliated Taihe Hospital of Hubei University of Medicine,Shiyan 442000,Hubei Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2022年第25期4084-4092,共9页
Chinese Journal of Tissue Engineering Research
基金
湖北省省教育厅项目(B2013108),项目负责人:郭广玲。
关键词
干细胞
小鼠
卵巢早衰
雌激素
卵泡刺激素
抗苗勒管激素
卵泡
META分析
stem cell
mice
ovarian failure
estrogen
follicle stimulating hormone
anti-mullerian hormone
follicle
meta-analysis
