摘要
自然流产是妇科常见病之一,不仅损害妇女的身心健康,甚至还可能会引发一系列家庭问题,而给社会带来不稳定因素。所以寻找一种防止流产的有效方法具有积极的临床意义和社会意义。
1.文献研究
目前大多数学者将Th1/Th2型细胞因子介导的免疫反应描述为Th1型免疫反应和Th2型免疫反应。细胞因子在病理妊娠丢失中有着重要作用。Th1细胞因子对妊娠有害,而Th2细胞因子却对维持妊娠起着积极作用。两者之间的平衡对维持正常妊娠起着重要的作用。平衡被打破,将导致疾病如自然流产的发生。
妊娠早期蜕膜中含大量淋巴细胞,γδT细胞数量较非妊娠期增加1倍。γδT细胞可根据不同的病原体刺激产生不同的细胞因子,进而影响Th1和Th2细胞的分化成熟,从而参与免疫调节。γδT细胞的许多生物学特点仍处于被探索阶段,但人们已发现γδT细胞的特性既与Th相似即分泌多种细胞因子,又与CTL相似即对多种细胞表现出细胞毒活性。已有资料显示TCRγδT细胞具有识别绒毛滋养细胞表达的人类白细胞抗原,参与调节Th1/Th2型细胞因子的平衡偏移,对母胎免疫的调节起着重要作用。
2.临床研究:母胎界面Th1/Th2细胞因子平衡与肾虚自然流产相关性的研究
所有病例均来源于2005年3月至2005年12月在广州中医药大学第一附属医院妇科门诊和住院部就诊的妇科病人。所有受试病例必须按照诊断标准、纳入标准和排除标准进行筛选。选择肾虚型早期自然流产的孕妇10例为实验组,正常早期妊娠的孕妇要求人工流产者10例为对照组。采用半定量RT-PCR检测蜕膜组织Th1型(IL-2、IFN-γ)/Th2型(IL-4、IL-10)细胞因子mRNA表达。
本研究再次证实妊娠期Th1/Th2细胞因子的平衡偏移与SA发生具有相关性,结果提示肾虚型自然流产患者母胎界面细胞因子Th1(IL-2、IFN-γ)/Th2(IL-10、IL-4)平衡失调可能是自然流产肾虚证的本质之一。本研究进一步为“肾主生殖”理论提供了科学依据,同时亦为健脾补肾法治疗该病提供了科学根据。
Spontaneous abortion is common diseases in the specialty of obstectrics and gynecology. Abortion not only injures the women' s mind and body health, even may cause a series of family problem and bring unsteady factor for society. So looking for a kind of valid method that prevent from abortion to have the actively clinical meaning and social meanings. 1. Literature ResearchMost of scholars described immune reaction mediated by Thl/Th2-type cytokine as Th1 immune reaction and Th2 immune reaction. Cytokines seem to play a critical role in the pathogenesis of pregnancy loss. Thl cytokines have been shown to exert deleterious effects on pregnancy, inhibiting foetal growth and development. On the other hand, Th2 cytokines have been associated with successful pregnancy. Balance between Thl immune reaction and Th2 immune reaction play an important role 'in retaining normal pregnancy. If the balance was broken, disease as spontaneous abortion will be induced.Deciduas contain bulk leukomonocyte and γ δ T-cells. The number of Y 8 T-cells in early pregnancy trimester is more than one times in non-gestation period. γ δ T-cells can bring about different cytokines by different factors, and affect differentiation and maturity of Thl/Th2-type cells to participate immunological regulation. Although many biological features of γ δ T-cells is still to remain in exploring stage, people have already found that features of γ δ T-cells resemble as both
Th(secreting many kinds of cytokine) and CTL(displaying cell poison). Many data disclosed that y 5 T-cells play an important roles in discriminating humam leucocyte antigen expressed by tomentum and nurse cells and regulating balance of Thl/Th2-type cytokines and fetomaternal interface immunity.2. Clinical Research: Research on the Correlations between the Balance of Cytokines and Kidney-Deficiency Spontaneous AbortionAll Cases were from the 1" Affiliated Hospital, Guangzhou University of TCM, from March to December in 2005. Cases were sieved according to diagnostic, internalize and depletion criteria. Experiment group concluded 10 patients who were diagnosed as spontaneous abo-rtion of kidney-deficiency or both kidney and spleen deficiency in the first trimester. Control group concluded 10 normal women in early pregnancy who requested artificial abortion. The expression of Thl/Th2-type cytokine mRNA in deciduas were detected by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR).The balance of cytokine Thl/Th2 was inclined to the side of Th2 in normal pregnancy. It was conformed that balance of Thl/Th2-type cytokines may beconcerned with kidney-deficiency spontaneous abortion and the part of essence .The research also demonstrated that the essence of kidney-deficiency spontaneous abortion was the disorder of fetomaternal interface cytokines balance. It also provided the scientic evidence of the theory of the kidney dominating reproduction, and of tonify-kidney and spleen therapy.3. Experimental Studies3.1 The Effect of Prescription Zhuyun- IE to Cytokines Thl/Th2 of Fetomaternal Interface in Kidney-Deficiency and Luteal Insufficiency Aborting RatsPregnant experimental rats wer-e randomly divided into 5 groups and every group concluded 8 SD rats. Kidney-deficiency and luteal insufficiency aborting rat model was established by Hydroxyurea and Mifepristone. The
model rats were fed with hydroxyurea 450mg/Kg daily and with mifepristone 3. 75 mg/kg at the seventh day for creating a kidney-deficiency and luteal insufficiency aborting rat model.A : model with pill of Duo li ma;B: model without herbs;C: model with high dose Prescription Zhuyun-IH;D: model with low dose Prescription Zhuyun-ffl;E: controlled group(fedwith saline instead of medicine). Under sterility condition , the expression of cytokines Thl/Th2 mRNA in deciduas were detected by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 30 minutes.It is disclosed that Prescription Zhuyun-III can invigorate the kidney and spleen, so that it can retrieved the disorder of cytokines Thl/Th2 of fetomaternal interface of in kidney-deficiency and luteal insufficiency, aborting rats. As a result, the rate of abortion degraded. Both high dosage and low dosage of Prescription Zhuyun-III were effective in the treatment. But high dosage of Prescription Zhuyun-IQ was more effective than the low dosage in its treatment and had some dose-effect relationship.3.2 The effect of Prescription Zhuyun-ITJ to Cytokines Thl/Th2 of Peripheral Blood in Kidney-Deficiency and Luteal Insufficiency Aborting RatsWe detected the serum interleukin-2(IL~2) .. interleukin-4(IL-4) > interleukin-10 (IL-10) -. interferon- y (IFN- Y) of the identical peripheral blood samples by enzyme-linked immunosorbent assay(ELISA).Group A, B, C and D, especially group B, showed some symptoms of kidney deficiency, such as withered and vacuous fur, slow action and less ability. The body weight of rats in each group before establishing kidney-deficiency and luteal insufficiency aborting rat model had no significant difference, P>0. 05. However after establishing kidney-deficiency and luteal insufficiency aborting rat model, the increasement of weight in group B
were the lowest, there was significantly different compared with other groups, KQ. 05. Both group C and group B can inhibited it. Group B was better than group C.The balance of cytokine Thl/Th2 was inclined to the side of THl in group B, and the rate of abortion increased. Both high dosage and low dosage of Prescription Zhuyun-IH were effective in the treatment and showed no difference from the Duo Li Ma group. But high dosage of Prescription Zhuyun-ffl was more effective than the low dosage in its treatment.3. 3 The Effect of Prescription Zhuyun-TU to TCR Y 8 T cells of Peripheral Blood in Kidney-deficiency and Luteal Insufficiency Aborting RatsThe research indicated that Prescription Zhuyun-ffl can invigorate the kidney and spleen . It also can adjust TCRy 8 T cell level and the proportionality of TCRy 6T /CD3T cells so that degrading the rate of abortion. But the effect of Prescription Zhuyun-ffl on fetomaternal interface still needed further investigating.4. Results(DThe balance of cytokine Thl/Th2 was inclined to the side of TH2 in normal pregnancy. It was conformed that balance of Thl/Th2-type cytokines may be concerned with kidney-deficiency spontaneous abortion and the part of essence . The research also demonstrated that the essence of kidney-deficiency spontaneous abortion was the disorder of fetomaternal interface cytokines balance. It also provided the scientic evidence of the theory of the kidney dominating reproduction, and of tonify-kidney and spleen therapy.(2)It is disclosed that Prescription Zhuyun-ffl can invigorate the kidney and spleen, so that it can retrieved the disorder of cytokines Thl/Th2 of fetomaternal interface and peripheral blood in kidney-deficiency and luteal insufficiency aborting rats. As a result, the rate of abortion degraded. Both high dosage and.low dosage of Prescription Zhuyun-IH were effective in the treatment. But high dosage of Prescription Zhuyun-III was more effective than the low dosage in its treatment and had some dose-effect relationship. Prescription Zhuyun-III increased peripheral blood and
fetomaternal interface cytokine levels . Prescription Zhuyun-ffl decreased Thl/Th2 lymphocyte ratios;thus, it modify the peripheral and fetomaternal interface Thl/Th2 balance. In comparison with Western medicine, TCM have an advantage in treatment and a bright future.(3)The research indicated that Prescription Zhuyun-ffl can adjust TCRy 8 T cell level and the proportionality of TCRy 8T /CD3T cells so that the rate of abortion degraded. The effect of Prescription Zhuyun-ITJ on fetomaternal interface still needed further investigating.
引文
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