脂联素通过p38MAPK信号通路影响URSA患者外周血AdipoR1和免疫细胞平衡  

Adiponectin affects the expression of peripheral blood AdipoR1 and immune cells populations in patients with URSA through p38MAPK signaling pathways

作　　者：李维宏[1] 牟晓玲[1] 漆洪波[1] LI Weihong;MOU Xiaoling;QI Hongbo(Department of Gynaecology and Obstetrics, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China)

机构地区：[1]重庆医科大学附属第一医院妇产科,400016

出　　处：《免疫学杂志》2018年第5期436-442,共7页Immunological Journal

基　　金：国家自然科学基金(81501335);重庆市卫计委医学科研项目(2017MSXM015)

摘　　要：目的探讨脂联素对不明原因复发性流产(URSA)患者外周血调节性T细胞(Treg)/Th17平衡调节、Adipo R和p38MAPK信号通路的影响。方法以URSA患者为研究对象,正常妊娠女性、健康未孕女性为对照,分离外周血单个核细胞(PBMC),RT-PCR检测Adipo R1/R2表达;脂联素体外干预后,ELISA法检测IL-17和TGF-β分泌水平,RT-PCR检测Adipo R1、Fox P3和RORγt m RNA表达,Western blot检测p38MAPK和p-p38MAPK表达;加入脂联素前先加入p38MAPK抑制剂SB203580,观察SB203580对Fox P3、RORγt、Adipo R1 m RNA表达水平的影响。结果 URSA患者Adipo R1显著降低;脂联素体外处理可升高URSA患者TGF-β分泌水平,降低IL-17水平,上调URSA患者Fox P3和Adipo R1 m RNA表达水平,降低RORγt表达水平,并呈明显的时间依赖性;脂联素可升高URSA患者p38MAPK激酶和p-p38MAPK激酶蛋白表达;p38MAPK抑制剂SB203580单独处理对Fox P3、RORγt和Adipo R1 m RNA表达无明显影响,但能明显抑制脂联素上调Fox P3和Adipo R1 m RNA和下调RORγt m RNA表达的作用。结论脂联素可能通过Adipo R1激活URSA患者体内p38MAPK信号通路改善Treg/Th17平衡而保护妊娠。Unexplained recurrent spontaneous abortion（URSA） is tightly related to abnormal maternal tolerance to the semi-allogenic fetus. This study was performed to investigate the effects of adiponectin on regulatory T cell（Treg）/Th17 balance, Adipo R expression and p38 MAPK signaling pathway in peripheral blood of patients with URSA. Peripheral blood mononuclear cells（PBMC） were isolated form URSA patients, normal pregnant women and healthy non-pregnancy women, and then AdipoR1/2 expression were measured by RT-PCR. After the treatment of adiponectin in vitro, the levles of IL-17 and TGF-β were detected by ELISA, the levels of AdipoR1,Fox P3 and RORγt were measured by RT-PCR, while p38 MAPK and p-p38 MAPK were detected by Western blotting.Furthermore, p38 MAPK inhibitor SB203580 was used to block the pathway, and Adipo R, Fox P3 and RORγt m RNA were measured to check the roles of p38 MAPK patheway in changes of T cell（Treg）/Th17 balance induced by adiponectin. Data showed that AdipoR1 level was significantly decreased in URSA patients. Adiponectin treatment increased TGF-β expression and reduced IL-17 expression. At the same time, adiponectin increased Fox P3 and AdipoR1 expression, reduce RORγt m RNA expression in URSA patients in a time-dependent manner. Adiponectin treatment also increased p38 MAPK and p-p38 MAPK expression in URSA patients. SB203580, a p38 MAPK inhibitor, had no influence on Fox P3, RORγt and AdipoR1 m RNA expression, but could inhibit the effect of adiponectin on these factors. In conclusion,adiponectin treatment can ameliorate the imbalance of Treg/Th17 in patients with URSA, suggesting that adiponectin may protect pregnancy by regulating the balance of Treg/Th17 related to AdipoR1 and the activation of p38 MAPK signaling pathway.

关 键 词：脂联素 不明原因复发性流产 Th17 调节性T细胞 P38MAPK 

分 类 号：R714.21[医药卫生—妇产科学]