湿热瘀阻型炎症性抗精子免疫性不孕的临床及实验研究
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摘要
目的:从病原体检测、免疫学、分子生物学等方面对湿热瘀阻型炎症性抗精子抗体阳性免疫性不孕症进行临床及实验研究,探讨本病的病因病理和发病机制,并观察清湿化瘀合剂治疗本病的临床疗效,探讨其可能的作用机理。并从动物实验中求证临床上已初步推测探讨出来的作用机理。通过模拟自然病理过程,建立生殖道炎症抗精子免疫动物模型,进一步探讨抗精子抗体产生的机理,以及抗精子抗体免疫性不孕的可能病因病理及发病机制。
方法:临床上对中医辨证为湿热瘀阻证,妇科检查诊断为慢性生殖道炎症的抗精子抗体免疫性不孕的患者,采用清湿化瘀合剂治疗3—6个月,观察临床疗效及用药前后临床症状,抗精子抗体(AsAb)、白细胞介数6(IL-6)、T淋巴细胞亚群水平的变化。实验方面,模拟自然病理发生的过程,建立生殖道炎症抗精子免疫动物模型:随机将实验新西兰兔分为5组,分别是:单纯炎症+生理盐水组(A组)、单纯免疫+生理盐水组(B组)、炎症免疫+清湿化瘀合剂治疗组(C组)、炎症免疫+生理盐水对照组(D组)、空白对照+生理盐水组(E组)。采用阴道插管到宫腔的方式,分别按不同模型注入混合细菌或/和人精子膜抗原,并对治疗组予清湿化瘀合剂灌胃治疗。实验(造模)前后分别观察新西兰兔体重、形态、饮食活动和阴道分泌物等情况:耳缘静脉采血,测血清AsAb、IL-6、肿瘤坏死因子-α(TNF-α)、血浆一氧化氮(NO)水平。实验后,取材子宫内膜,取子宫内膜匀浆,检查一氧化氮合酶(NOS)和诱导型一氧化氮合酶(iNOS)活性水平。
结果:清湿化瘀合剂治疗湿热瘀阻炎症性抗精子抗体免疫性不孕的妊娠率为20%,治愈率为35%,临床有效率为60%(20例)。本药能有效降低血清抗精子抗体,白介素6水平,使淋巴细胞CD8~+比率增高,CD4~+和CD4~+/CD8~+比率降低,恢复机体正常免疫。动物实验证明局部生殖道的感染和免疫均能产生抗精子抗体,而且两者具有协同作用。炎症性抗精子免疫动物体内存在异常升高的IL-6、TNF-α、NO、NOS活性和iNOS活性,而且其水平与血清AsAb水平存在正相关。清湿化瘀合剂能有效降低和清除血清AsAb,降低异常升高的IL-6、TNF-α、NO、NOS活性和iNOS活性,清除体内异常的炎症反应,调节机体免疫平衡。
Objective:1 , To explore on female Inflammatory and Immunological Infertility with antiSperm antibody( AsAb in brief) positive probing on Damp-heat and Blood Stasis Syndrome in terms of the examination of pathogen, immunology and molecular biology. Try to understand its etiologic factor, pathology, pathogenesis of the disease.2, To observe the clinical efficacy of "Qing Shi Hua Yu Mixture" (QSHY in brief) on female Inflammatory and Immunological Infertility with AsAb positive probing on Damp-heat and Blood Stasis Syndrome, and try to analyze the possible mechanism of the treatment.3 , To establish an experimental animal model of inflammatory and AsAb positive rabbits by the means of simulating the course of natural pathology. To further explore the formative mechanism of AsAb, and its possible etiologic factor, pathology and pathogenesis of infertility with AsAb positive . Method:On clinic research. 20 patients according with the diagnostic standards which were classified to Immunological Infertility with AsAb positive probing on Damp-heat and Blood Stasis Syndrome and had been diagnosed as Chronic Genital Tube Inflammatory by Gynecological Check had been treated by QSHY for more than 3 months to 6 months. Then we compared the symptoms and signs, the vary levels of AsAb、 Subgroup of T lymphocytes, Nk cells and Interleukin-6 at the beginning and end of the treatment.In the animal experiment, to establish an animal model of inflammatory and AsAb positive rabbits by means of imitating the course of natural pathology. The New Zealand rabbits were randomly divided into 5 groups, these were the pure inflammatory group, the pure immunological group、 the inflammatory plus immunological treatment group, the inflammatory plus immunological model group and the control group.
方法:临床上对中医辨证为湿热瘀阻证,妇科检查诊断为慢性生殖道炎症的抗精子抗体免疫性不孕的患者,采用清湿化瘀合剂治疗3—6个月,观察临床疗效及用药前后临床症状,抗精子抗体(AsAb)、白细胞介数6(IL-6)、T淋巴细胞亚群水平的变化。实验方面,模拟自然病理发生的过程,建立生殖道炎症抗精子免疫动物模型:随机将实验新西兰兔分为5组,分别是:单纯炎症+生理盐水组(A组)、单纯免疫+生理盐水组(B组)、炎症免疫+清湿化瘀合剂治疗组(C组)、炎症免疫+生理盐水对照组(D组)、空白对照+生理盐水组(E组)。采用阴道插管到宫腔的方式,分别按不同模型注入混合细菌或/和人精子膜抗原,并对治疗组予清湿化瘀合剂灌胃治疗。实验(造模)前后分别观察新西兰兔体重、形态、饮食活动和阴道分泌物等情况:耳缘静脉采血,测血清AsAb、IL-6、肿瘤坏死因子-α(TNF-α)、血浆一氧化氮(NO)水平。实验后,取材子宫内膜,取子宫内膜匀浆,检查一氧化氮合酶(NOS)和诱导型一氧化氮合酶(iNOS)活性水平。
结果:清湿化瘀合剂治疗湿热瘀阻炎症性抗精子抗体免疫性不孕的妊娠率为20%,治愈率为35%,临床有效率为60%(20例)。本药能有效降低血清抗精子抗体,白介素6水平,使淋巴细胞CD8~+比率增高,CD4~+和CD4~+/CD8~+比率降低,恢复机体正常免疫。动物实验证明局部生殖道的感染和免疫均能产生抗精子抗体,而且两者具有协同作用。炎症性抗精子免疫动物体内存在异常升高的IL-6、TNF-α、NO、NOS活性和iNOS活性,而且其水平与血清AsAb水平存在正相关。清湿化瘀合剂能有效降低和清除血清AsAb,降低异常升高的IL-6、TNF-α、NO、NOS活性和iNOS活性,清除体内异常的炎症反应,调节机体免疫平衡。
Objective:1 , To explore on female Inflammatory and Immunological Infertility with antiSperm antibody( AsAb in brief) positive probing on Damp-heat and Blood Stasis Syndrome in terms of the examination of pathogen, immunology and molecular biology. Try to understand its etiologic factor, pathology, pathogenesis of the disease.2, To observe the clinical efficacy of "Qing Shi Hua Yu Mixture" (QSHY in brief) on female Inflammatory and Immunological Infertility with AsAb positive probing on Damp-heat and Blood Stasis Syndrome, and try to analyze the possible mechanism of the treatment.3 , To establish an experimental animal model of inflammatory and AsAb positive rabbits by the means of simulating the course of natural pathology. To further explore the formative mechanism of AsAb, and its possible etiologic factor, pathology and pathogenesis of infertility with AsAb positive . Method:On clinic research. 20 patients according with the diagnostic standards which were classified to Immunological Infertility with AsAb positive probing on Damp-heat and Blood Stasis Syndrome and had been diagnosed as Chronic Genital Tube Inflammatory by Gynecological Check had been treated by QSHY for more than 3 months to 6 months. Then we compared the symptoms and signs, the vary levels of AsAb、 Subgroup of T lymphocytes, Nk cells and Interleukin-6 at the beginning and end of the treatment.In the animal experiment, to establish an animal model of inflammatory and AsAb positive rabbits by means of imitating the course of natural pathology. The New Zealand rabbits were randomly divided into 5 groups, these were the pure inflammatory group, the pure immunological group、 the inflammatory plus immunological treatment group, the inflammatory plus immunological model group and the control group.
引文
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