胎元饮合寿胎丸加减联合主动免疫治疗不明原因复发性流产患者的疗效及其对辅助性T淋巴细胞17/调节性T淋巴细胞免疫失衡的影响
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摘要
目的:探讨胎元饮合寿胎丸加减治疗不明原因复发性流产患者的临床效果及其机制。方法:选择2015年1月至2016年3月收治的96例不明原因复发性流产(URSA)患者,根据随机数表法分为对照组和观察组,每组48例。对照组给予主动免疫治疗,观察组采用胎元饮合寿胎丸加减联合主动免疫治疗。比较两组的妊娠成功率及妊娠结局。测定并比较两组外周血Th17细胞,Treg细胞,炎症因子白细胞介素(IL)-4,IL-10,IL-17,Th17,Treg转录因子维甲酸相关孤核受体γt(RORγt),Fox P3 mRNA表达水平。比较两组治疗中不良反应发生情况。结果:对照组再次妊娠率95.8%,与观察组的97.9%比较差异无统计学意义。观察组的妊娠成功率93.8%(45/48),明显高于对照组的77.1%(37/48)(P<0.05)。观察组的足月分娩比例为95.6%,明显高于对照组的81.1%(P<0.05)。治疗后两组的Th17/CD4+,Th17/Treg较本组治疗前明显降低,Treg/CD4+较本组治疗前明显升高(P<0.05),且观察组的变化程度较对照组更加明显(P<0.05)。治疗后两组的IL-4,IL-10水平均较本组治疗前上升,IL-17水平降低(P<0.05);治疗后观察组IL-4,IL-10水平较对照组高,IL-17水平较对照组低(P<0.05)。治疗后两组RORγt mRNA表达水平较本组治疗前降低,Fox P3 mRNA表达水平较本组治疗前升高(P<0.05);观察组Fox P3,RORγt mRNA变化水平较对照组更加明显(P<0.05)。所有患者均无明显不良反应发生。结论:采用胎元饮合寿胎丸加减联合主动免疫治疗不明原因复发性流产疗效确切,其机制可能通过调节炎性因子水平,改善Th17/Treg的免疫失衡状态,进而改善妊娠结局,降低流产率,且安全性较高,治疗成本低,值得临床推广应用。
Objective: To investigate the clinical efficacy and mechanism of Taiyuanyin and Shoutaiwan in patients with recurrent recurrent spontaneous abortion. Method: A total of 96 patients with recurrent recurrent spontaneous abortion( URSA) from January 2015 to March 2016 in our hospital were selected and divided into control group and observation group according to the random number table method,48 cases in each group. The control group received active immunotherapy, and the observation group was treated with Taiyuanyin and Shoutaiwan combined with active immunotherapy. The pregnancy success rate and pregnancy outcome were compared between these two groups. The mRNA expression levels of Th17 cells,Treg cells,inflammatory factors interleukin( IL)-4,IL-10,IL-17,Th17, Treg transcription factor RORγt and Fox P3 were measured and compared between two groups. The incidence of adverse reactions was also compared. Result: The repregnancy rate was 95. 8% in control group and 97. 9% in observation group,with no statistical difference between two groups.The success rate of pregnancy was 93. 8%( 45/48) in observation group,significantly higher than 77. 1%( 37/48) in control group( P < 0. 05). The percentage of term delivery was 95. 6% in observation group,significantly higher than 81. 1% in control group( P < 0. 05). The ratios of Th17/CD4+and Th17/Treg after treatment were significantly decreased in both groups,and Treg/CD4+was significantly increased( P < 0. 05),and the changes in observation group were more obvious than those in control group( P < 0. 05). After treatment,the levels of IL-4 and IL-10 were increased in both groups,and the level of IL-17 was decreased( P < 0. 05). After treatment,the levels of IL-4 and IL-10 in observation group were higher than those in control group,and the level of IL-17 was lower than that in control group( P < 0. 05). The expression level of RORγt mRNA was reduced and the expression level of Fox P3 mRNA was increased after treatment in both groups( P < 0. 05),and the changes in observation group were more obvious than those in control group( P < 0. 05). No adverse reactions were found in any patient. Conclusion: Taiyuanyin and Shoutaiwan combined with active immunotherapy for unexplained recurrent spontaneous abortion has clear efficacy. It can improve the imbalance of Th17/Treg by regulating the level of inflammatory factors,thus improving the outcome of pregnancy and reducing the abortion rate. In addition,it has high safety and low cost,worthy of clinical application.
Objective: To investigate the clinical efficacy and mechanism of Taiyuanyin and Shoutaiwan in patients with recurrent recurrent spontaneous abortion. Method: A total of 96 patients with recurrent recurrent spontaneous abortion( URSA) from January 2015 to March 2016 in our hospital were selected and divided into control group and observation group according to the random number table method,48 cases in each group. The control group received active immunotherapy, and the observation group was treated with Taiyuanyin and Shoutaiwan combined with active immunotherapy. The pregnancy success rate and pregnancy outcome were compared between these two groups. The mRNA expression levels of Th17 cells,Treg cells,inflammatory factors interleukin( IL)-4,IL-10,IL-17,Th17, Treg transcription factor RORγt and Fox P3 were measured and compared between two groups. The incidence of adverse reactions was also compared. Result: The repregnancy rate was 95. 8% in control group and 97. 9% in observation group,with no statistical difference between two groups.The success rate of pregnancy was 93. 8%( 45/48) in observation group,significantly higher than 77. 1%( 37/48) in control group( P < 0. 05). The percentage of term delivery was 95. 6% in observation group,significantly higher than 81. 1% in control group( P < 0. 05). The ratios of Th17/CD4+and Th17/Treg after treatment were significantly decreased in both groups,and Treg/CD4+was significantly increased( P < 0. 05),and the changes in observation group were more obvious than those in control group( P < 0. 05). After treatment,the levels of IL-4 and IL-10 were increased in both groups,and the level of IL-17 was decreased( P < 0. 05). After treatment,the levels of IL-4 and IL-10 in observation group were higher than those in control group,and the level of IL-17 was lower than that in control group( P < 0. 05). The expression level of RORγt mRNA was reduced and the expression level of Fox P3 mRNA was increased after treatment in both groups( P < 0. 05),and the changes in observation group were more obvious than those in control group( P < 0. 05). No adverse reactions were found in any patient. Conclusion: Taiyuanyin and Shoutaiwan combined with active immunotherapy for unexplained recurrent spontaneous abortion has clear efficacy. It can improve the imbalance of Th17/Treg by regulating the level of inflammatory factors,thus improving the outcome of pregnancy and reducing the abortion rate. In addition,it has high safety and low cost,worthy of clinical application.
引文
[1]刘佳杰,方小武,陈捷,等.高龄男性精子质量与不明原因复发性流产相关性分析[J].中国性科学,2017,26(6):107-109.
[2]贾新转,张娜,郭丽娜,等.不明原因复发性流产患者月经血和外周血NK细胞亚群水平变化及意义[J].山东医药,2016,56(21):60-62.
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[7]吕春红,王连珠.丙种球蛋白联合淋巴细胞主动免疫治疗复发性流产的疗效[J].实用临床医药杂志,2016,20(7):96-98.
[8]陈雷宁,裘毓雯,欧湘红,等.异体淋巴细胞免疫治疗不明原因复发性流产巢式病例对照研究[J].实用妇产科杂志,2014,30(4):295-298.
[9]赵伟,秦小佩,方雯,等.加味胎元饮配合黄体酮治疗早期先兆流产的临床研究[J].中医临床研究,2012,4(11):90-91.
[10]王力,闻姬,韩彩艳,等.寿胎丸调节原因不明复发性自然流产患者免疫失衡机制[J].北京中医药大学学报,2012,35(11):781-785.
[11]丰有吉,沈铿.妇产科学[M].2版.北京:人民卫生出版社,2005:69.
[12]欧阳惠卿.中医妇科学[M].北京:人民卫生出版社,2002.
[13]黄剑青,陈惠霞,叶敏仪,等.淋巴细胞主动免疫治疗不明原因复发性流产患者治疗效果观察[J].安徽医药,2014,18(5):872-873,874.
[14]王晓艳,景军宁,王文弟,等.淋巴细胞免疫治疗不明原因复发性流产妊娠结局分析[J].兰州大学学报:医学版,2013,39(1):30-32,36.
[15]毛姝雯,夏天.复发性流产的免疫性因素研究新进展[J].河北医科大学学报,2015,36(1):117-119.
[16]郭兰娇,王孟丽,兰芳.主动免疫治疗对复发性流产患者血液相关指标的影响研究[J].中国妇幼保健,2016,31(9):1934-1936.
[17]罗振宇,柴冬宁,李萍,等.复发性流产病因分析及免疫治疗[J].中国妇幼保健,2016,31(4):782-784.
[18]沈华,韩丽娟,张文红,等.复发性流产的中医治疗进展[J].世界中西医结合杂志,2014,9(6):674-676.
[19]党慧敏,刘艳巧,刘润侠,等.补肾活血方联合地屈孕酮对复发性流产患者临床疗效及Th1/Th2型细胞因子的影响[J].西安交通大学学报:医学版,2014,35(6):832-836.
[20]郑加永,张红萍,徐晓敏,等.人类白细胞抗原DQ基因多态性与不明原因复发性流产的关联分析[J].中华医学遗传学杂志,2016,33(1):81-84.
[21]陈媛妮,苏慧森.八珍益母汤治疗闭经一例[J].河南中医,2012,32(5):653.
[22]ZHU X M,HUANG Y M,FAN J F,et al.Aberrant frequency of IL-10-producing B cells and its association with the balance of Treg/Th17 in children with inflammatory bowel disease[J].Die Pharmazie,2015,70(10):656-660.
[23]高云,王涛,高月平,等.加味升降散对饮停胸胁型结核性胸膜炎患者胸腔积液ADA,外周血Treg细胞及DC细胞亚群的影响[J].中国实验方剂学杂志,2017,23(12):173-177.
[24]李维宏,牟晓玲.黄体酮保胎治疗对不明原因复发性流产患者外周血辅助性T淋巴细胞17/调节性T淋巴细胞免疫失衡的影响研究[J].中国全科医学,2015,18(36):4444-4449.
[2]贾新转,张娜,郭丽娜,等.不明原因复发性流产患者月经血和外周血NK细胞亚群水平变化及意义[J].山东医药,2016,56(21):60-62.
[3]ZHU L Y,CHEN X,XU Z Z,et al.Changes and clinical significance of peripheral blood helper T lymphocyte and natural killer(NK)cells in unexplained recurrent spontaneous abortion(URSA)patients after abortion and successful pregnancy[J].Clin Exp Obstet Gynecol,2015,42(1):62-66.
[4]吴彤华,朱元昌,尹彪,等.不明原因复发性流产与HLA-DQ相关性的初步研究[J].中国免疫学杂志,2013,29(9):955-959.
[5]蒋艳萍,曹来英,洛若愚,等.Th17细胞和Treg细胞与不明原因复发性流产的关系[J].武汉大学学报:医学版,2011,32(6):773-777.
[6]陈静,李慕军,黄千贻,等.不明原因复发性流产患者外周血及蜕膜组织中Th17细胞相关效应细胞因子的表达及意义[J].实用临床医药杂志,2015,19(9):91-93.
[7]吕春红,王连珠.丙种球蛋白联合淋巴细胞主动免疫治疗复发性流产的疗效[J].实用临床医药杂志,2016,20(7):96-98.
[8]陈雷宁,裘毓雯,欧湘红,等.异体淋巴细胞免疫治疗不明原因复发性流产巢式病例对照研究[J].实用妇产科杂志,2014,30(4):295-298.
[9]赵伟,秦小佩,方雯,等.加味胎元饮配合黄体酮治疗早期先兆流产的临床研究[J].中医临床研究,2012,4(11):90-91.
[10]王力,闻姬,韩彩艳,等.寿胎丸调节原因不明复发性自然流产患者免疫失衡机制[J].北京中医药大学学报,2012,35(11):781-785.
[11]丰有吉,沈铿.妇产科学[M].2版.北京:人民卫生出版社,2005:69.
[12]欧阳惠卿.中医妇科学[M].北京:人民卫生出版社,2002.
[13]黄剑青,陈惠霞,叶敏仪,等.淋巴细胞主动免疫治疗不明原因复发性流产患者治疗效果观察[J].安徽医药,2014,18(5):872-873,874.
[14]王晓艳,景军宁,王文弟,等.淋巴细胞免疫治疗不明原因复发性流产妊娠结局分析[J].兰州大学学报:医学版,2013,39(1):30-32,36.
[15]毛姝雯,夏天.复发性流产的免疫性因素研究新进展[J].河北医科大学学报,2015,36(1):117-119.
[16]郭兰娇,王孟丽,兰芳.主动免疫治疗对复发性流产患者血液相关指标的影响研究[J].中国妇幼保健,2016,31(9):1934-1936.
[17]罗振宇,柴冬宁,李萍,等.复发性流产病因分析及免疫治疗[J].中国妇幼保健,2016,31(4):782-784.
[18]沈华,韩丽娟,张文红,等.复发性流产的中医治疗进展[J].世界中西医结合杂志,2014,9(6):674-676.
[19]党慧敏,刘艳巧,刘润侠,等.补肾活血方联合地屈孕酮对复发性流产患者临床疗效及Th1/Th2型细胞因子的影响[J].西安交通大学学报:医学版,2014,35(6):832-836.
[20]郑加永,张红萍,徐晓敏,等.人类白细胞抗原DQ基因多态性与不明原因复发性流产的关联分析[J].中华医学遗传学杂志,2016,33(1):81-84.
[21]陈媛妮,苏慧森.八珍益母汤治疗闭经一例[J].河南中医,2012,32(5):653.
[22]ZHU X M,HUANG Y M,FAN J F,et al.Aberrant frequency of IL-10-producing B cells and its association with the balance of Treg/Th17 in children with inflammatory bowel disease[J].Die Pharmazie,2015,70(10):656-660.
[23]高云,王涛,高月平,等.加味升降散对饮停胸胁型结核性胸膜炎患者胸腔积液ADA,外周血Treg细胞及DC细胞亚群的影响[J].中国实验方剂学杂志,2017,23(12):173-177.
[24]李维宏,牟晓玲.黄体酮保胎治疗对不明原因复发性流产患者外周血辅助性T淋巴细胞17/调节性T淋巴细胞免疫失衡的影响研究[J].中国全科医学,2015,18(36):4444-4449.