丙种球蛋白联合地屈孕酮治疗复发性流产的效果及对患者免疫功能和血清炎症因子水平的影响
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摘要
目的:探讨丙种球蛋白联合地屈孕酮治疗复发性流产的效果及对患者免疫功能和血清炎症因子水平的影响。方法:选择2016年1月-2017年12月我院收治的82例复发性流产患者为研究对象,将其随机分为两组。对照组采用单纯口服地屈孕酮,每次10 mg,每天2次;观察组在对照组基础上联合静脉滴注丙种球蛋白500 mg/(kg·d)。比较两组治疗前后的血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)以及白介素-10(IL-10)水平,CD4~+/CD8~+、CD8~+以及CD4~+及保胎成功率。结果:治疗后,观察组治愈14例,有效18例,无效9例,治疗有效率为78.05%(32/41),明显高于对照组[60.98%(25/41)](P<0.05);两组治疗后的血清TNF-α、CD8~+水平较治疗前明显降低(P<0.05),血清IL-6、IL-10、CD4~+/CD8~+以及CD4~+水平较治疗前明显升高(P<0.05),且观察组血清TNF-α、CD8~+水平明显低于对照组(P<0.05),血清IL-6、IL-10、CD4~+/CD8~+以及CD4~+水平明显高于对照组(P<0.05)。观察组的保胎成功率为82.93%(34/41),明显高于对照组[31.71%(13/41)](P<0.05)。结论:丙种球蛋白联合地屈孕酮可以有效增强复发性流产患者体内的免疫功能,减少调节炎症因子的表达,提高保胎成功率.
Objective: To investigate the effect of gamma globulin combined with megestrol acetate in the treatment of recurrent spontaneous abortion and its influence on immune function and serum inflammatory factors. Methods: 82 patients with recurrent spontaneous abortion admitted to our hospital from January 2016 to December 2017 were randomly divided into two groups. The control group was treated with oral megestrol acetate only, and the observation group was given intravenous gamma globulin [500 mg/(kg·d)] on the basis of the control group. The serum levels of IL-6, TNF-α and IL-10, CD4~+/CD8~+, CD8~+, CD4~+, and the success rate of pregnancy preservation were compared between the two groups. Results: After treatment, 14 cases were cured, 18 cases were effective and 9 cases were ineffective in the observation group. The effective rate was 78.05%(32/41), which was significantly higher than that in the control group [60.98%(25/41)](P<0.05). And the levels of serum TNF-α and CD8~+in the two groups were significantly lower than those be-fore treatment(P<0.05), the levels of serum IL-6, IL-10, CD4~+/CD8~+and CD4~+were significantly higher than those before treatment(P<0.05). The levels of serum TNF-α and CD8~+in the observation group were significantly lower than those in the control group(P<0.05). The levels of serum IL-6, IL-10, CD4~+/CD8~+and CD4~+in the observation group were significantly higher than those in the control group(P<0.05). The success rate of the observation group was 82.93%(34/41), which was significantly higher than that of the control group [31.71%(13/41)](P<0.05). Conclusion: Gamma globulin combined with megestrol acetate can effectively enhance the immune function of patients with recurrent spontaneous abortion, reduce the expression of inflammatory factors, and improve the success rate of pregnancy preservation.
Objective: To investigate the effect of gamma globulin combined with megestrol acetate in the treatment of recurrent spontaneous abortion and its influence on immune function and serum inflammatory factors. Methods: 82 patients with recurrent spontaneous abortion admitted to our hospital from January 2016 to December 2017 were randomly divided into two groups. The control group was treated with oral megestrol acetate only, and the observation group was given intravenous gamma globulin [500 mg/(kg·d)] on the basis of the control group. The serum levels of IL-6, TNF-α and IL-10, CD4~+/CD8~+, CD8~+, CD4~+, and the success rate of pregnancy preservation were compared between the two groups. Results: After treatment, 14 cases were cured, 18 cases were effective and 9 cases were ineffective in the observation group. The effective rate was 78.05%(32/41), which was significantly higher than that in the control group [60.98%(25/41)](P<0.05). And the levels of serum TNF-α and CD8~+in the two groups were significantly lower than those be-fore treatment(P<0.05), the levels of serum IL-6, IL-10, CD4~+/CD8~+and CD4~+were significantly higher than those before treatment(P<0.05). The levels of serum TNF-α and CD8~+in the observation group were significantly lower than those in the control group(P<0.05). The levels of serum IL-6, IL-10, CD4~+/CD8~+and CD4~+in the observation group were significantly higher than those in the control group(P<0.05). The success rate of the observation group was 82.93%(34/41), which was significantly higher than that of the control group [31.71%(13/41)](P<0.05). Conclusion: Gamma globulin combined with megestrol acetate can effectively enhance the immune function of patients with recurrent spontaneous abortion, reduce the expression of inflammatory factors, and improve the success rate of pregnancy preservation.
引文
[1]Dong X,Long Y,Hui W.miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion(RSA)[J].Gynecological Endocrinology,2017,33(4):274-278
[2]Sun Q,Zhang X L.Research on apoptotic signaling pathways of recurrent spontaneous abortion caused by dysfunction of trophoblast infiltration[J].European Review for Medical&Pharmacological Sciences,2017,21(3 Suppl):12
[3]Ramu D,Venkatesan V,Paul S F D,et al.Genetic variation in matrix metalloproteinase MMP2,and MMP9,as a risk factor for idiopathic recurrent spontaneous abortions in an Indian population[J].Journal of Assisted Reproduction&Genetics,2017,34(2):1-5
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[5]Li J,Xu D,Li H L.Evaluation of failed immunotherapy among patients with negative APLA recurrent spontaneous abortion by serum anticardiolipin antibodies and mononuclear cell of Tim-1[J].European Review for Medical&Pharmacological Sciences,2017,21(5):908
[6]Lee H J,Park T C,Kim J H,et al.The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion:A Systematic Review and Meta-Analysis[J].BioMed Research International,2017,2017(9):1-10
[7]Quan X,Yang X.Correlation between unexplained recurrent spontaneous abortion with CD4+CD25+regulatory T-cell and killer cell immunoglobulin-like receptor levels[J].Experimental&Therapeutic Medicine,2017,14(2):1459-1462
[8]Barmettler S,Otani I M,Minhas J,et al.Gastrointestinal Manifestations in X-linked Agammaglobulinemia[J].Journal of Clinical Immunology,2017,37(3):287-294
[9]Wang G,Sun J.Interactive Effects of Snps Located Within CD28/B7Pathway and Environment on Susceptibility to Recurrent Spontaneous Abortion[J].Cellular Physiology&Biochemistry,2017,43(6):2185-2199
[10]Ning L,Li S,Wang Y,et al.Decreased expression of WNT2 in villi of unexplained recurrent spontaneous abortion patients may cause trophoblast cell dysfunction via downregulated Wnt/β-catenin signaling pathway[J].Cell Biology International,2017,41(8):898
[11]Nonaka T,Tominaga M,Takahashi M,et al.Immunotherapy with paternal lymphocytes for patients with unexplained recurrent abortion and association with blocking antibodies:Comparison between patient groups with primary and secondary unexplained recurrent abortion[J].Journal of Reproductive Medicine,2018,63(3):285-291
[12]Petrányi G,Simsa P,á.Padányi,et al.Intravenous immunoglobulin and partner specific thrombocyte transfusion immunotherapy in selected cases of recurrent miscarriage[J].Journal of Reproductive Medicine,2018,63(1):13-20
[13]Zhao X,Jiang Y,Wang L,et al.Advances in Understanding the Immune Imbalance between T-Lymphocyte Subsets and NK Cells in Recurrent Spontaneous Abortion[J].Geburtshilfe Und Frauenheilkunde,2018,78(07):677-683
[14]Healy M,Patounakis G,Zanelotti A,et al.Does premature elevated progesterone on the day of trigger increase spontaneous abortion rates in fresh and subsequent frozen embryo transfers[J].Gynecological Endocrinology,2017,33(6):472-475
[15]Khalid A,Qureshi H J,Nazir S,et al.Effect of second hand smoke exposure on serum estradiol and progesterone levels in women having first trimester spontaneous abortions[J].Pakistan Journal of Medical&Health Sciences,2017,11(1):163-167
[16]Moffuouk S,Yahia M,Mouffouk C,et al.Accuracy of serum markers,progesterone and vitamins measurements for early screening of abortions in the eastern region of Algeria(Batna)[J].2018,90(2):126-129
[17]Weinberger T,Maglione P,Cunningham-Rundles C.Differences in Pulmonary Complications in Common Variable Immunodeficiency and X-Linked Agammaglobulinemia[J].Journal of Allergy&Clinical Immunology,2017,139(2):AB111
[18]Benali M,Yang J,Chan K W,et al.Homozygous TCF3 mutation is associated with severe hypogammaglobulinemia and B-cell acute lymphoblastic leukemia[J].J Allergy Clin Immunol,2017,140(4):1191
[19]Pac M,Bernatowska E A,Kierku J,et al.Gastrointestinal disorders next to respiratory infections as leading symptoms of X-linked agammaglobulinemia in children-34-year experience of a single center[J].Archives of Medical Science Ams,2017,13(2):412-417
[20]Li J,Xu D,Li H L.Evaluation of failed immunotherapy among patients with negative APLA recurrent spontaneous abortion by serum anticardiolipin antibodies and mononuclear cell of Tim-1[J].European Review for Medical&Pharmacological Sciences,2017,21(5):908
[21]Ye S L,Gu X K,Tao L Y,et al.Efficacy of Different Treatment Regimens for Antiphospholipid Syndrome-related Recurrent Spontaneous Abortion[J].Chinese Medical Journal,2017,130(12):1395-1399
[22]Eaa C,Giardino G,Worth A,et al.Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab[J].International Reviews of Immunology,2017,36(6):1-8
[23]Kempf B,Edgar J D,Mc C C,et al.Nitazoxanide Is an Ineffective Treatment of Chronic Norovirus in Patients With X-Linked Agammaglobulinemia and May Yield False-Negative Polymerase Chain Reaction Findings in Stool Specimens[J].Journal of Infectious Diseases,2017,215(3):486-487
[24]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 hCG combined with immunoglobulin[J].Experimental&Therapeutic Medicine,2017,14(2):1114-1118
[25]Zhu L,Chen H,Liu M,et al.Treg/Th17 Cell Imbalance and IL-6 Profile in Patients With Unexplained Recurrent Spontaneous Abortion[J].Reproductive Sciences,2017,24(6):882-890
[26]Chen Z,Li Y X,Fu H J,et al.Hepatitis B Virus Core Antigen Stimulates IL-6 Expression via p38,ERK and NF-κB Pathways in Hepatocytes[J].Cellular Physiology&Biochemistry International Journal of Experimental Cellular Physiology Biochemistry&Pharmacology,2017,41(1):91
[27]Li S,Wang L,Xing Z,et al.Expression level of TNF-αin decidual tissue and peripheral blood of patients with recurrent spontaneous abortion[J].Central-European Journal of Immunology,2017,42(2):156-160
[28]Rahmani S A,Paknejad Z,Mohammadkhanlou M.The effects of tumor necrosis factor-α(TNF-α)and IL-1 receptor antagonist(IL-1Ra)polymorphisms on recurrent abortion in Azari women[J].Ginekologia Polska,2017,88(8):421-427
[29]Blois S M,Freitag N,Tiradogonzález I,et al.NK cell-derived IL-10is critical for DC-NK cell dialogue at the maternal-fetal interface[J].Scientific Reports,2017,7(1):2189
[30]Vidyadhari M,Sujatha M,Krupa P,et al.Haplotype analysis of IL-10gene polymorphism in couples with spontaneous abortions and aborted fetuses[J].Immunologic Research,2017,65(4):853-861
[2]Sun Q,Zhang X L.Research on apoptotic signaling pathways of recurrent spontaneous abortion caused by dysfunction of trophoblast infiltration[J].European Review for Medical&Pharmacological Sciences,2017,21(3 Suppl):12
[3]Ramu D,Venkatesan V,Paul S F D,et al.Genetic variation in matrix metalloproteinase MMP2,and MMP9,as a risk factor for idiopathic recurrent spontaneous abortions in an Indian population[J].Journal of Assisted Reproduction&Genetics,2017,34(2):1-5
[4]Bari觢i A,Pereza N,Hod觩i A,et al.A Single Nucleotide Polymorphism of DNA methyltransferase 3B gene is a risk factor for recurrent spontaneous abortion[J].American Journal of Reproductive Immunology,2017,78(953-963):e12765
[5]Li J,Xu D,Li H L.Evaluation of failed immunotherapy among patients with negative APLA recurrent spontaneous abortion by serum anticardiolipin antibodies and mononuclear cell of Tim-1[J].European Review for Medical&Pharmacological Sciences,2017,21(5):908
[6]Lee H J,Park T C,Kim J H,et al.The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion:A Systematic Review and Meta-Analysis[J].BioMed Research International,2017,2017(9):1-10
[7]Quan X,Yang X.Correlation between unexplained recurrent spontaneous abortion with CD4+CD25+regulatory T-cell and killer cell immunoglobulin-like receptor levels[J].Experimental&Therapeutic Medicine,2017,14(2):1459-1462
[8]Barmettler S,Otani I M,Minhas J,et al.Gastrointestinal Manifestations in X-linked Agammaglobulinemia[J].Journal of Clinical Immunology,2017,37(3):287-294
[9]Wang G,Sun J.Interactive Effects of Snps Located Within CD28/B7Pathway and Environment on Susceptibility to Recurrent Spontaneous Abortion[J].Cellular Physiology&Biochemistry,2017,43(6):2185-2199
[10]Ning L,Li S,Wang Y,et al.Decreased expression of WNT2 in villi of unexplained recurrent spontaneous abortion patients may cause trophoblast cell dysfunction via downregulated Wnt/β-catenin signaling pathway[J].Cell Biology International,2017,41(8):898
[11]Nonaka T,Tominaga M,Takahashi M,et al.Immunotherapy with paternal lymphocytes for patients with unexplained recurrent abortion and association with blocking antibodies:Comparison between patient groups with primary and secondary unexplained recurrent abortion[J].Journal of Reproductive Medicine,2018,63(3):285-291
[12]Petrányi G,Simsa P,á.Padányi,et al.Intravenous immunoglobulin and partner specific thrombocyte transfusion immunotherapy in selected cases of recurrent miscarriage[J].Journal of Reproductive Medicine,2018,63(1):13-20
[13]Zhao X,Jiang Y,Wang L,et al.Advances in Understanding the Immune Imbalance between T-Lymphocyte Subsets and NK Cells in Recurrent Spontaneous Abortion[J].Geburtshilfe Und Frauenheilkunde,2018,78(07):677-683
[14]Healy M,Patounakis G,Zanelotti A,et al.Does premature elevated progesterone on the day of trigger increase spontaneous abortion rates in fresh and subsequent frozen embryo transfers[J].Gynecological Endocrinology,2017,33(6):472-475
[15]Khalid A,Qureshi H J,Nazir S,et al.Effect of second hand smoke exposure on serum estradiol and progesterone levels in women having first trimester spontaneous abortions[J].Pakistan Journal of Medical&Health Sciences,2017,11(1):163-167
[16]Moffuouk S,Yahia M,Mouffouk C,et al.Accuracy of serum markers,progesterone and vitamins measurements for early screening of abortions in the eastern region of Algeria(Batna)[J].2018,90(2):126-129
[17]Weinberger T,Maglione P,Cunningham-Rundles C.Differences in Pulmonary Complications in Common Variable Immunodeficiency and X-Linked Agammaglobulinemia[J].Journal of Allergy&Clinical Immunology,2017,139(2):AB111
[18]Benali M,Yang J,Chan K W,et al.Homozygous TCF3 mutation is associated with severe hypogammaglobulinemia and B-cell acute lymphoblastic leukemia[J].J Allergy Clin Immunol,2017,140(4):1191
[19]Pac M,Bernatowska E A,Kierku J,et al.Gastrointestinal disorders next to respiratory infections as leading symptoms of X-linked agammaglobulinemia in children-34-year experience of a single center[J].Archives of Medical Science Ams,2017,13(2):412-417
[20]Li J,Xu D,Li H L.Evaluation of failed immunotherapy among patients with negative APLA recurrent spontaneous abortion by serum anticardiolipin antibodies and mononuclear cell of Tim-1[J].European Review for Medical&Pharmacological Sciences,2017,21(5):908
[21]Ye S L,Gu X K,Tao L Y,et al.Efficacy of Different Treatment Regimens for Antiphospholipid Syndrome-related Recurrent Spontaneous Abortion[J].Chinese Medical Journal,2017,130(12):1395-1399
[22]Eaa C,Giardino G,Worth A,et al.Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab[J].International Reviews of Immunology,2017,36(6):1-8
[23]Kempf B,Edgar J D,Mc C C,et al.Nitazoxanide Is an Ineffective Treatment of Chronic Norovirus in Patients With X-Linked Agammaglobulinemia and May Yield False-Negative Polymerase Chain Reaction Findings in Stool Specimens[J].Journal of Infectious Diseases,2017,215(3):486-487
[24]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 hCG combined with immunoglobulin[J].Experimental&Therapeutic Medicine,2017,14(2):1114-1118
[25]Zhu L,Chen H,Liu M,et al.Treg/Th17 Cell Imbalance and IL-6 Profile in Patients With Unexplained Recurrent Spontaneous Abortion[J].Reproductive Sciences,2017,24(6):882-890
[26]Chen Z,Li Y X,Fu H J,et al.Hepatitis B Virus Core Antigen Stimulates IL-6 Expression via p38,ERK and NF-κB Pathways in Hepatocytes[J].Cellular Physiology&Biochemistry International Journal of Experimental Cellular Physiology Biochemistry&Pharmacology,2017,41(1):91
[27]Li S,Wang L,Xing Z,et al.Expression level of TNF-αin decidual tissue and peripheral blood of patients with recurrent spontaneous abortion[J].Central-European Journal of Immunology,2017,42(2):156-160
[28]Rahmani S A,Paknejad Z,Mohammadkhanlou M.The effects of tumor necrosis factor-α(TNF-α)and IL-1 receptor antagonist(IL-1Ra)polymorphisms on recurrent abortion in Azari women[J].Ginekologia Polska,2017,88(8):421-427
[29]Blois S M,Freitag N,Tiradogonzález I,et al.NK cell-derived IL-10is critical for DC-NK cell dialogue at the maternal-fetal interface[J].Scientific Reports,2017,7(1):2189
[30]Vidyadhari M,Sujatha M,Krupa P,et al.Haplotype analysis of IL-10gene polymorphism in couples with spontaneous abortions and aborted fetuses[J].Immunologic Research,2017,65(4):853-861