重组脂联素对自然流产模型小鼠妊娠结局及Th17/Treg平衡的影响

Effect of Recombinant Adiponectin on Pregnancy Outcome and Th17/Treg Balance in Spontaneous Abortion Mice Model

目的探究重组脂联素(APN)对自然流产(SA)模型小鼠妊娠结局及辅助性T细胞17(Th17)/调节性T细胞(Treg)平衡的影响。方法将雌性CBA/J小鼠与雄性BALB/c小鼠交配建立正常妊娠(NP)模型(n=10),雌性CBA/J小鼠与雄性DBA/2小鼠交配建立SA模型(n=20),造模成功后,将20只SA模型小鼠随机分为脂联素组(APN组,n=10)和生理盐水组(NS组,n=10),妊娠第5d,APN组腹腔注射10μg/(kg·d)重组脂联素,1次/d,NP组和NS组腹腔注射等量生理盐水,3组疗程为9 d。疗程结束,眼球取血,检测血清中白细胞介素17(IL-17)、脂联素、转化生长因子β(TGF-β)、IL-17/TGF-β水平;处死孕鼠,计算胚胎吸收率,检测脾脏淋巴细胞中Th17/Treg细胞分群。结果与NP组比较,NS组胚胎吸收率及血清中IL-17、IL-17/TGF-β水平及Th17/CD4+T细胞比例、Th17/Treg比值明显升高(P<0.05),血清中脂联素、TGF-β水平及Treg/CD4+T细胞比例明显下降(P<0.05);与NS组比较,APN组胚胎吸收率及血清中IL-17、IL-17/TGF-β水平及Th17/CD4+T细胞比例、Th17/Treg比值明显下降(P<0.05),血清中脂联素、TGF-β水平及Treg/CD4+T细胞比例明显升高(P<0.05);NP组、APN组胚胎吸收率及血清中脂联素、IL-17、TGF-β、IL-17/TGF-β水平及脾脏淋巴细胞中Th17、Treg细胞分群比较,差异无统计学意义(P>0.05)。结论重组脂联素治疗可能通过纠正Th17/Treg细胞失衡及相关细胞因子水平,改善SA模型小鼠的妊娠结局。

Objective To investigate the effect of recombinant adiponectin(APN)on pregnancy outcome and helper T cell 17(Th17)/regulatory T cell(Treg)balance in spontaneous abortion(SA)mice model.Methods The normal pregnancy(NP,n=10)and SA model(n=20)were respectively induced with CBA/J x BALB/c and CBA/J x DBA/2.The mice with SA were randomly divided into APN group(n=10)and normal saline group(NS group,n=10).On the 5th day of pregnancy,APN group was intraperitoneally injected with 10μg/(kg·d)APN once daily for 9d,NP group and NS group were intraperitoneally injected with the same amount of normal saline for 9d.At the end of the treatment,the serum levels of interleukin-17(IL-17),adiponectin(APN),transforming growth factor beta(TGF-β),and IL-17/TGF-βwere measured.The embryo absorption rate was calculated and the Th17/Treg cell population was also detected in the spleen lymphocytes.Results The embryo absorption rate and serum IL-17,IL-17/TGF-βlevels,Th17/CD4+T cell ratio,and Th17/Treg ratio of the NS group was significantly higher than those of the NP group and APN group(P<0.05),with no statistic difference between the NP group and APN group(P>0.05).The levels of TGF-βand Treg/CD4+T cells of the NS group was significantly lower than those of the NP group and APN group(P<0.05),with no statistic difference between the NP group and APN group(P>0.05).Conclusion The application of recombinant adiponectin may improve pregnancy outcome in SA model mice by correcting Th17/Treg cell imbalance and related cytokine levels.