不明原因复发性流产患者蜕膜及外周血中IL-15、IL-22的表达及补肾活血方对其影响的观察
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摘要
目的观察不明原因复发性流产(URSA)患者蜕膜及外周血中IL-15、IL-22的表达情况及补肾活血方对其的影响。方法试验一:纳入样本30例,分为实验组(患URSA且妊娠失败)与正常对照组(正常妊娠行人工流产),每组15例;应用RT-PCR法测定两组受试者蜕膜组织中IL-15R和IL-22R的mRNA含量。试验二:将60例患URSA且再次妊娠的患者,随机分为治疗组和对照组,每组30例;治疗组予补肾活血方+地屈孕酮,对照组予地屈孕酮。两组疗程均为4周,观察近期疗效及妊娠结局,比较外周血中IL-15与IL-22水平的变化情况。结果 (1)RT-PCR显示,实验组蜕膜组织中IL-15R、IL-22R的表达较正常对照组明显升高(P<0.05)。(2)治疗前,两组外周血IL-15、IL-22水平差异无统计学意义(P>0.05)。治疗前后组内比较,两组IL-15、IL-22水平均明显降低(P<0.05)。组间治疗后比较,治疗组IL-15、IL-22水平明显低于对照组(P<0.05)。(3)治疗组、对照组总有效率分别为93.33%、73.33%;组间近期疗效比较,治疗组明显优于对照组(P<0.05)。(4)治疗组、对照组流产率分别为6.67%、26.67%;组间流产率比较,治疗组明显低于对照组(P<0.05)。结论 URSA的发生可能与蜕膜中IL-15R和IL-22R的高表达有关。同时,补肾活血方可明显下调URSA患者外周血中IL-15、IL-22的水平,其机制可能是通过调节妊娠期母体免疫耐受,从而有利于妊娠的维持,并减少流产的发生。
Objective To observe the expression of IL-15 and IL-22 in decidua and peripheral blood and the effect of Bushen Huoxue Recipe on it in patients with unexplained recurrent spontaneous abortion( URSA). Methods Trial 1: 30 patients were enrolled and assigned into the experimental group( patients with URSA and pregnancy failure) and the normal control group( patients with normal pregnancy and induced abortion),15 patients in each group; and the mRNA levels of IL-15 R and IL-22 R in decidual tissues of the subjects in the two groups were determined by RT-PCR. Trial 2: 60 patients with URSA and re-pregnancy were randomly assigned into the treatment group and the control group,30 patients in each group; and the treatment group was treated with Bushen Huoxue Recipe + dydrogesterone,while the control group was treated with dydrogesterone. Both groups were treated for 4 weeks,and the short-term efficacy and pregnancy outcome were observed. Changes in the levels of IL-15 and IL-22 in peripheral blood were compared. Results(1) RT-PCR showed that the expression of IL-15 R and IL-22 R in decidual tissues of subjects in the experimental group was significantly higher than that in the normal control group( P<0.05).(2) There was no significant difference in the levels of IL-15 and IL-22 between the groups before treatment( P>0.05). The levels decreased significantly in both groups before and after treatment( P>0.05). After treatment,the levels were significantly lower in the treatment group than in the control group( P<0.05).(3) The total effective rate was 93.33% and 73.33% in the treatment group and the control group respectively; and the short-term efficacy in the treatment group was significantly superior to that in the control group( P<0.05).(4) The abortion rate was 6.67% and 26.67% in the treatment group and the control group respectively. It was significantly lower in the treatment group than in the control group( P<0.05). Conclusion The occurrence of URSA may be related to the high expression of IL-15R and IL-22R in the decidua. At the same time,Bushen Huoxue Recipe significantly down-regulates the levels of IL-15 and IL-22 in peripheral blood of patients with URSA. The mechanism of action may be regulation of maternal immune tolerance during pregnancy,thereby facilitating maintenance of pregnancy and reducing the incidence of abortion.
Objective To observe the expression of IL-15 and IL-22 in decidua and peripheral blood and the effect of Bushen Huoxue Recipe on it in patients with unexplained recurrent spontaneous abortion( URSA). Methods Trial 1: 30 patients were enrolled and assigned into the experimental group( patients with URSA and pregnancy failure) and the normal control group( patients with normal pregnancy and induced abortion),15 patients in each group; and the mRNA levels of IL-15 R and IL-22 R in decidual tissues of the subjects in the two groups were determined by RT-PCR. Trial 2: 60 patients with URSA and re-pregnancy were randomly assigned into the treatment group and the control group,30 patients in each group; and the treatment group was treated with Bushen Huoxue Recipe + dydrogesterone,while the control group was treated with dydrogesterone. Both groups were treated for 4 weeks,and the short-term efficacy and pregnancy outcome were observed. Changes in the levels of IL-15 and IL-22 in peripheral blood were compared. Results(1) RT-PCR showed that the expression of IL-15 R and IL-22 R in decidual tissues of subjects in the experimental group was significantly higher than that in the normal control group( P<0.05).(2) There was no significant difference in the levels of IL-15 and IL-22 between the groups before treatment( P>0.05). The levels decreased significantly in both groups before and after treatment( P>0.05). After treatment,the levels were significantly lower in the treatment group than in the control group( P<0.05).(3) The total effective rate was 93.33% and 73.33% in the treatment group and the control group respectively; and the short-term efficacy in the treatment group was significantly superior to that in the control group( P<0.05).(4) The abortion rate was 6.67% and 26.67% in the treatment group and the control group respectively. It was significantly lower in the treatment group than in the control group( P<0.05). Conclusion The occurrence of URSA may be related to the high expression of IL-15R and IL-22R in the decidua. At the same time,Bushen Huoxue Recipe significantly down-regulates the levels of IL-15 and IL-22 in peripheral blood of patients with URSA. The mechanism of action may be regulation of maternal immune tolerance during pregnancy,thereby facilitating maintenance of pregnancy and reducing the incidence of abortion.
引文
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[7]潘琳,冯晓玲,张璇.免疫型复发性流产现代中西医治疗进展[J].湖北中医杂志,2016,38(8):80-82.
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[9]FENG D,PARK O,RADAEVA S,et al.Interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway[J].Int J Biol Sci,2012,8(2):249-257.
[10]MITRA A,RAYCHAUDHURI S K,RAYCHAUDHURI S P.IL-22induced cell prolife-ration is regulated by PI3K/Akt/m TORsignalingcascade[J].Cytokine,2012,60(1):38-42.
[11]BRODNAHAN M M,MILLER D C,ADAMS M,et al.IL-22 is expressed by the invasive trophoblast of the equine(Equus caballus)chorionic girdle[J].J Immunol,2012,188(9):4181-4187.
[12]MARIO G,LUIGI I,GAETANO C,et al.Regulatory T cells,inflammation,and endoplasmic reticulum stress in women with defective endometrial receptivity[J].Fertility and sterility,2015,103(6):1579-1586.
[13]党慧敏,刘艳巧,刘润霞,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.
[14]苏健球,刘桂英.孕前益肾活血中药联合孕后安胎治疗不明原因复发性流产肾虚血瘀证30例[J].湖南中医杂志,2018,34(7):85-86.
[2]张杨,王玲,李娜,等.补肾活血方对不明原因复发性流产小鼠蜕膜细胞TNFR1、PI3K/Bcx-xl的影响[J].中华中医药杂志,2017,32(2):768-771.
[3]林其德.复发性流产免疫学诊断和治疗共识[J].生殖医学杂志,2008,17(1):4-5.
[4]谈媛,李国华,张勤华.朱氏补肾活血方对肾虚血瘀型复发性流产合并抗磷脂综合征患者妊娠结局的影响[J].上海中医药杂志,2018,52(8):61-64.
[5]国家中医药管理局.中医病证诊断疗效标准[M].南京:南京大学出版社,1994:243.
[6]徐新亚,张科群,徐子宁.益母固肾汤联合主动免疫治疗不明原因复发性流产的疗效及其对患者免疫功能的影响[J].上海中医药杂志,2018,52(7):63-65.
[7]潘琳,冯晓玲,张璇.免疫型复发性流产现代中西医治疗进展[J].湖北中医杂志,2016,38(8):80-82.
[8]徐春美,吕玲,于晓妮.血浆TNF-α、IL-15、IL-10在子痫前期中的作用[J].吉林医学,2014,35(34):7580-7582.
[9]FENG D,PARK O,RADAEVA S,et al.Interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway[J].Int J Biol Sci,2012,8(2):249-257.
[10]MITRA A,RAYCHAUDHURI S K,RAYCHAUDHURI S P.IL-22induced cell prolife-ration is regulated by PI3K/Akt/m TORsignalingcascade[J].Cytokine,2012,60(1):38-42.
[11]BRODNAHAN M M,MILLER D C,ADAMS M,et al.IL-22 is expressed by the invasive trophoblast of the equine(Equus caballus)chorionic girdle[J].J Immunol,2012,188(9):4181-4187.
[12]MARIO G,LUIGI I,GAETANO C,et al.Regulatory T cells,inflammation,and endoplasmic reticulum stress in women with defective endometrial receptivity[J].Fertility and sterility,2015,103(6):1579-1586.
[13]党慧敏,刘艳巧,刘润霞,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.
[14]苏健球,刘桂英.孕前益肾活血中药联合孕后安胎治疗不明原因复发性流产肾虚血瘀证30例[J].湖南中医杂志,2018,34(7):85-86.
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