外周血HMGB1水平与不明原因复发性流产患者Th17/Treg平衡的关系
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摘要
目的探讨外周血中高迁移率族蛋白B1(HMGB1)水平与不明原因复发性流产患者辅助性T细胞17(Th17/调节性T(Treg)细胞平衡的关系。方法选择2016年1月～2018年1月在湖北省妇幼保健院(以下简称"我院")进行治疗的不明原因复发性流产患者83例为观察组,选择同期在我院进行产前检查的健康孕妇80名为对照组。入院后采集两组受试者的空腹静脉血,采用流式细胞仪检测其Th17、Treg细胞水平,并进行组间比较。采用酶联免疫吸附试验(ELISA)检测两组受试者的HMGB1、晚期糖基化终产物受体(RAGE)、白细胞介素-6(IL-6)、IL-10、IL-17、转化生长因子-β(TGF-β)水平。并探讨HMGB1与各细胞及细胞因子表达的相关性。结果观察组HMGB1、RAGE、Th17、Th17/Treg水平高于对照组,其Treg水平低于对照组,差异有高度统计学意义(P <0.01)。观察组IL-6、IL-17水平高于对照组,IL-10、TGF-β水平低于对照组,差异有高度统计学意义(P <0.01)。Pearson相关性分析显示,HMGB1与Th17、Th17/Treg、RAGE、IL-6、IL-17水平呈正相关(r=0.456、0.489、0.528、0.397、0.438,均P <0.05),与Treg、IL-10、TGF-β水平呈负相关(r=-0.552、-0.523、-0.439,均P <0.05)。结论不明原因复发性流产患者的外周血中HMGB1水平与Th17/Treg平衡间有一定的相关性,HMGB1、Th17、Treg的异常表达及Th17/Treg失衡可能参与了不明原因复发性流产的发生。
Objective To investigate the relationship between the high mobility group box protein B1(HMGB1) level in peripheral blood and the helper T cell 17(Th17)/regulatory T(Treg) cell balance in patients with unexplained recurrent spontaneous abortion. Methods From January 2016 to January 2018, 83 patients with unexplained recurrent abortion who were treated in Hubei Maternal and Child Health Hospital( "our hospital" for short) were selected as the observation group, and 80 healthy pregnant women who underwent prenatal examination in our hospital during the same period were selected as the control group. Fasting venous blood was collected after admission. Th17 and Treg cell levels were measured by flow cytometry and compared between the two groups. The levels of Th17 and Treg cells were detected by flow cytometry and compared between groups. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of HMGB1, advanced glycation end product receptor(RAGE), interleukin-6(IL-6), IL-10, IL-17, and transforming growth factor-β(TGF-β). The relationship between HMGB1 and the expression of various cells and cytokines was also investigated. Results The levels of HMGB1, RAGE, Th17 and Th17/Treg in the observation group were higher than those in the control group, and the Treg was lower than that in the control group, and the difference was highly statistically significant(P < 0.01). The levels of IL-6 and IL-17 in the observation group were higher than those in the control group, and the levels of IL-10 and TGF-β were lower than those in the control group, and the difference was highly statistically significant(P < 0.01). Pearson correlation analysis showed that HMGB1 was positively correlated with Th17,Th17/Treg, RAGE, IL-6, IL-17 levels(r = 0.456,0.489, 0.528, 0.397, 0.438, P < 0.05). There was a negative correlation between the levels of HMGB1 and Treg, IL-10 and TGF-β(r =-0.552,-0.523,-0.439,P < 0.05). Conclusion There is a certain correlation between HMGB1 level and Th17/Treg balance in peripheral blood of patients with unexplained recurrent abortion. The abnormal expression of HMGB1, Th17 and Treg and the imbalance of Th17/Treg may be involved in the occurrence of unexplained recurrent abortion.
Objective To investigate the relationship between the high mobility group box protein B1(HMGB1) level in peripheral blood and the helper T cell 17(Th17)/regulatory T(Treg) cell balance in patients with unexplained recurrent spontaneous abortion. Methods From January 2016 to January 2018, 83 patients with unexplained recurrent abortion who were treated in Hubei Maternal and Child Health Hospital( "our hospital" for short) were selected as the observation group, and 80 healthy pregnant women who underwent prenatal examination in our hospital during the same period were selected as the control group. Fasting venous blood was collected after admission. Th17 and Treg cell levels were measured by flow cytometry and compared between the two groups. The levels of Th17 and Treg cells were detected by flow cytometry and compared between groups. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of HMGB1, advanced glycation end product receptor(RAGE), interleukin-6(IL-6), IL-10, IL-17, and transforming growth factor-β(TGF-β). The relationship between HMGB1 and the expression of various cells and cytokines was also investigated. Results The levels of HMGB1, RAGE, Th17 and Th17/Treg in the observation group were higher than those in the control group, and the Treg was lower than that in the control group, and the difference was highly statistically significant(P < 0.01). The levels of IL-6 and IL-17 in the observation group were higher than those in the control group, and the levels of IL-10 and TGF-β were lower than those in the control group, and the difference was highly statistically significant(P < 0.01). Pearson correlation analysis showed that HMGB1 was positively correlated with Th17,Th17/Treg, RAGE, IL-6, IL-17 levels(r = 0.456,0.489, 0.528, 0.397, 0.438, P < 0.05). There was a negative correlation between the levels of HMGB1 and Treg, IL-10 and TGF-β(r =-0.552,-0.523,-0.439,P < 0.05). Conclusion There is a certain correlation between HMGB1 level and Th17/Treg balance in peripheral blood of patients with unexplained recurrent abortion. The abnormal expression of HMGB1, Th17 and Treg and the imbalance of Th17/Treg may be involved in the occurrence of unexplained recurrent abortion.
引文
[1]仇笑笑,何泽现,王健,等.HMGB1与原因不明复发性流产的关系[J].免疫学杂志,2016,29(4):346-350.
[2]Zhu L,Chen H,Liu M,et al.Treg/Th17 Cell Imbalance and IL-6 Profile in Patients With Unexplained Recurrent Spontaneous Abortion[J].Reprod Sci,2017,24(6):882-890.
[3]沙静,刘福民,王文,等.免疫球蛋白联合绒毛膜促性腺激素对原因不明复发性流产患者外周血Th17/Treg平衡的影响[J].中华临床医师杂志:电子版,2014,8(1):75-79.
[4]徐浩,吴淋淋,袁青,等.Th17/Treg细胞及其细胞因子在原因不明性复发性流产发病中的作用[J].中国卫生检验杂志,2016,38(17):2506-2508.
[5]邱勇华,熊员焕.原因不明复发性流产Th1/Th2/Th17/Treg免疫失衡的研究[J].赣南医学院学报,2016,36(6):925-928.
[6]杨丽,唐明燕,徐珍珍,等.不明原因复发性流产患者再次妊娠早孕期外周血Treg及Th17细胞与妊娠结局关系的研究[J].中华检验医学杂志,2017,40(3):174-179.
[7]Roomandeh N,Saremi A,Arasteh J,et al.Comparing Serum Levels of Th17 and Treg Cytokines in Women with Unexplained Recurrent Spontaneous Abortion and Fertile Women[J].Iran J Immunol,2018,15(1):59-67.
[8]吴金玉,冯晓玲.Th1/Th2、Th17/Treg平衡与原因不明复发性流产相关性的研究进展[J].国际检验医学杂志,2017,38(22):3156-3159.
[9]Jing S,Liu F,Zhai J,et al.Alteration of Th17 and Foxp3+regulatory T cells in patients with unexplained recurrent spontaneous abortion before and after the therapy of HCGcombined with immunoglobulin[J].Exp Ther Med,2017,14(2):1114-1118.
[10]高燕,王萍玲,张志军.不明原因复发性流产母胎界面蜕膜组织NK细胞及T淋巴细胞亚群的变化[J].武汉大学学报:医学版,2018,39(1):128-131.
[11]石琳.IL-7对不明原因复发性流产小鼠模型外周Th17/Treg、CD4+CD8+T淋巴细胞以及妊娠结局的影响[J].中国妇幼保健,2016,31(2):390-392.
[12]王健,杨晶,穆雅琴,等.外周血HMGB1经RAGE-IL-6途径调控Th17/Treg参与子痫前期的发病[J].中华微生物学和免疫学杂志,2018,32(2):1209-1212.
[13]张涛,连若纯,林嘉音,等.环孢素A对不明原因复发性流产患者外周血IFN-γ、TNF-α的调控[J].生殖医学杂志,2017,26(3):244-248.
[14]杨丽,唐明燕,徐珍珍,等.不明原因复发性流产患者再次妊娠早孕期外周血Treg及Th17细胞与妊娠结局关系的研究[J].中华检验医学杂志,2017,40(3):174-179.
[15]Madkour A,Bouamoud N,Louanjli N,et al.Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures[J].Zygote,2016,24(1):58-69.
[16]张晓姗.静脉用免疫球蛋白联合补肾化瘀汤治疗原因不明复发性自然流产的疗效及对血栓前状态和外周血Th17/Treg免疫失衡的影响[J].现代中西医结合杂志,2017,26(35):3903-3905.
[17]张珺,杨菁.Th17/Treg免疫失衡与原因不明复发性流产关系的研究进展[J].生殖医学杂志,2015,24(11):960-964.
[18]武卫华,濮玉江,张琳,等.外周血中HMGB1水平与不明复发性流产患者Th17/Treg细胞的关系[J].中国妇幼保健,2018,33(11):2541-2543.
[19]周天,丁家望,郑霞霞.高迁移率族蛋白B1对Th17/Treg平衡的调节[J].医学综述,2015,21(14):2519-2521.
[20]陈丹,孟昱时.Th17和Treg细胞在不明原因复发性流产中的研究进展[J].中国生育健康杂志,2016,27(3):296-297.
[21]Ding JW,Zheng XX,Zhou T,et al.HMGB1Modulates the Treg/Th17 Ratio in Atherosclerotic Patients[J].J Atheroscler Thromb,2016,23(6):737-745.
[2]Zhu L,Chen H,Liu M,et al.Treg/Th17 Cell Imbalance and IL-6 Profile in Patients With Unexplained Recurrent Spontaneous Abortion[J].Reprod Sci,2017,24(6):882-890.
[3]沙静,刘福民,王文,等.免疫球蛋白联合绒毛膜促性腺激素对原因不明复发性流产患者外周血Th17/Treg平衡的影响[J].中华临床医师杂志:电子版,2014,8(1):75-79.
[4]徐浩,吴淋淋,袁青,等.Th17/Treg细胞及其细胞因子在原因不明性复发性流产发病中的作用[J].中国卫生检验杂志,2016,38(17):2506-2508.
[5]邱勇华,熊员焕.原因不明复发性流产Th1/Th2/Th17/Treg免疫失衡的研究[J].赣南医学院学报,2016,36(6):925-928.
[6]杨丽,唐明燕,徐珍珍,等.不明原因复发性流产患者再次妊娠早孕期外周血Treg及Th17细胞与妊娠结局关系的研究[J].中华检验医学杂志,2017,40(3):174-179.
[7]Roomandeh N,Saremi A,Arasteh J,et al.Comparing Serum Levels of Th17 and Treg Cytokines in Women with Unexplained Recurrent Spontaneous Abortion and Fertile Women[J].Iran J Immunol,2018,15(1):59-67.
[8]吴金玉,冯晓玲.Th1/Th2、Th17/Treg平衡与原因不明复发性流产相关性的研究进展[J].国际检验医学杂志,2017,38(22):3156-3159.
[9]Jing S,Liu F,Zhai J,et al.Alteration of Th17 and Foxp3+regulatory T cells in patients with unexplained recurrent spontaneous abortion before and after the therapy of HCGcombined with immunoglobulin[J].Exp Ther Med,2017,14(2):1114-1118.
[10]高燕,王萍玲,张志军.不明原因复发性流产母胎界面蜕膜组织NK细胞及T淋巴细胞亚群的变化[J].武汉大学学报:医学版,2018,39(1):128-131.
[11]石琳.IL-7对不明原因复发性流产小鼠模型外周Th17/Treg、CD4+CD8+T淋巴细胞以及妊娠结局的影响[J].中国妇幼保健,2016,31(2):390-392.
[12]王健,杨晶,穆雅琴,等.外周血HMGB1经RAGE-IL-6途径调控Th17/Treg参与子痫前期的发病[J].中华微生物学和免疫学杂志,2018,32(2):1209-1212.
[13]张涛,连若纯,林嘉音,等.环孢素A对不明原因复发性流产患者外周血IFN-γ、TNF-α的调控[J].生殖医学杂志,2017,26(3):244-248.
[14]杨丽,唐明燕,徐珍珍,等.不明原因复发性流产患者再次妊娠早孕期外周血Treg及Th17细胞与妊娠结局关系的研究[J].中华检验医学杂志,2017,40(3):174-179.
[15]Madkour A,Bouamoud N,Louanjli N,et al.Intrauterine insemination of cultured peripheral blood mononuclear cells prior to embryo transfer improves clinical outcome for patients with repeated implantation failures[J].Zygote,2016,24(1):58-69.
[16]张晓姗.静脉用免疫球蛋白联合补肾化瘀汤治疗原因不明复发性自然流产的疗效及对血栓前状态和外周血Th17/Treg免疫失衡的影响[J].现代中西医结合杂志,2017,26(35):3903-3905.
[17]张珺,杨菁.Th17/Treg免疫失衡与原因不明复发性流产关系的研究进展[J].生殖医学杂志,2015,24(11):960-964.
[18]武卫华,濮玉江,张琳,等.外周血中HMGB1水平与不明复发性流产患者Th17/Treg细胞的关系[J].中国妇幼保健,2018,33(11):2541-2543.
[19]周天,丁家望,郑霞霞.高迁移率族蛋白B1对Th17/Treg平衡的调节[J].医学综述,2015,21(14):2519-2521.
[20]陈丹,孟昱时.Th17和Treg细胞在不明原因复发性流产中的研究进展[J].中国生育健康杂志,2016,27(3):296-297.
[21]Ding JW,Zheng XX,Zhou T,et al.HMGB1Modulates the Treg/Th17 Ratio in Atherosclerotic Patients[J].J Atheroscler Thromb,2016,23(6):737-745.
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