活血消异方治疗子宫内膜异位症的临床观察及实验研究

发布时间：2019-07-02 09:50

【摘要】：研究目的1观察及评价活血消异方治疗卵巢子宫内膜异位囊肿的临床疗效。2通过建立EM盆腔粘连大鼠模型,观察EM对大鼠盆腔粘连形成的影响及对TGF-β1/Smad3信号传导通路的调控,探讨活血消异方对EM盆腔粘连改善的机理,为EM相关盆腔粘连的临床治疗提供实验依据。研究方法1临床研究：采用病例自身前后对照研究的方法,以OEM患者为研究对象,予活血消异方加减治疗6个月经周期,比较治疗前后患者囊肿体积、VAS痛经、COX痛经症状、月经情况、慢性盆腔痛、CA125和CA199变化、妊娠情况等,评价活血消异方改善卵巢子宫内膜异位囊肿的临床疗效。2实验研究：采用自体移植将子宫内膜移植于肠系膜上的方法,建立EM盆腔粘连大鼠模型,观察盆腔粘连形成发展过程及模型成熟时间。造模后,随机分为模型组、中药组、西药组、空白组及假手术组,中西药组内分为造模术后第1天、第3天、第5天给药组,共9个组。中药组予活血消异方灌胃干预治疗,模型组、空白组、假手术组予等量的生理盐水灌胃,西药组肌注GnRH-α(达菲林)干预治疗。连续给药28天后,分别取材,采用免疫组化、RT-PCR法检测造模大鼠粘连腹膜组织及空白组正常腹膜组织中TGF-β1、Smad3的蛋白和基因表达。结果1临床研究(1)囊肿体积：服药3个月经周期和服药6个月经周期后,囊肿均显著小于治疗前(P0.05),右侧囊肿显著小于治疗前(P0.05),左侧囊肿治疗前后无显著性差异。(2)VAS痛经：VAS痛经程度及痛经持续时间均随服药周期延长而逐渐降低及缩短,治疗后各个周期VAS痛经程度均比治疗前极显著降低(P0.01)；对缩短痛经持续时间疗效相对较慢,服药4个月经周期后才表现出显著差异；在缓解痛经程度方面,中药对单纯OEM组较OEM合并腺肌症组疗效相对较快,在缩短痛经时间方面,两组疗效相当,均服药4个月经周期后才表现出显著差异。(3)COX痛经症状：COX症状严重程度及持续时间均随治疗周期延长逐渐减轻及缩短,其中小腹疼痛、背(腰骶)痛、乏力、易激惹症状治疗前后有极显著差异(P0.01)；食欲不振、头痛、失眠、抑郁症状治疗前后有显著差异(P0.05)。(4)CPP症状：CPP临床症状随服药时间延长逐渐减轻,中药对单纯OEM组疗效优于OEM合并腺肌症组,单纯OEM组服药1个月经周期后CPP症状积分较治疗前极显著降低(P0.01),而OEM合并腺肌症组服药4个月经周期后才出现显著性差异。(5)月经量：月经量过多症状随服药时间延长逐渐减轻,服药6个月经周期后月经量积分均值降低至正常范围内。(6)经色经质：活血消异方对经色经质异常有一定改善作用,服药5个月经周期后与治疗前有显著差异(P0.05)。(7) CA125、CA199:活血消异方对血清CA125、CA199阳性者下调效果不理想。(8)妊娠率：活血消异方能促进OEM患者妊娠。2实验研究(1)采用自身移植将子宫内膜移植于肠粘膜上的建模方法,模型成功率达100%；造模术后第5天大鼠模型为本实验研究最合适的EM盆腔粘连大鼠模型。(2)EM盆腔粘连大鼠粘连腹膜组织TGF-β1、Smad3的蛋白和基因表达量较假手术组显著升高(P0.01),中药组、西药组各组大鼠粘连腹膜组织TGF-β1、 Smad3基因和蛋白表达量较模型组均显著降低(P0.01),但仍高于假手术组(P0.05),中药组药物干预越早,盆腔粘连评分越低,TGF-β1基因和蛋白表达越低,组间比较均有统计学差异(P0.05),西药组药物干预时间与TGF-β1、 Smad3蛋白及基因表达均未表现出相应趋势。结论1临床观察：活血消异方能缩减OEM体积,减缓疼痛症状(痛经及CPP),改善月经情况,促进生育能,但下调血清CA125、CA199水平不理想。2实验研究：EM可导致严重、广泛的盆腔粘连；活血消异方能通过降调TGF-β1/Smad3信号传导,改善EM盆腔粘连程度,且中药干预越早,改善盆腔粘连程度疗效越显著。
[Abstract]:Objective: To observe and evaluate the clinical effect of Huoxue Xiaotang on the treatment of endometriosis in the ovary of the ovary. The effect of EM on the formation of pelvic adhesion in rats and the regulation of the conduction path of TGF-1/ Smad3 signal were observed by establishing an EM pelvic adhesion rat model. The mechanism of the improvement of the adhesion of Huoxue to the EM pelvic adhesion is discussed, and the experimental basis for the clinical treatment of the pelvic adhesion of the EM is provided. The clinical study of study method 1: using the method of the control study before and after the case itself, using the OEM patient as the study object, the blood circulation and elimination prescription is used for the treatment of 6 menstrual cycles, and the volume of the cyst of the patients before and after the treatment, the symptoms of the pain of the VAS, the symptoms of the COX-2, the menstrual situation and the chronic pelvic pain are compared, CA125 and CA199 changes, pregnancy and the like, evaluate the clinical effect of Huoxue Xiaohefang to improve the ectopic cyst of the ovary of the ovary. Experimental study: The method of autograft to transplant the endometrium to the mesentery is used to establish the model of the EM pelvic adhesion rat. The development of pelvic adhesion formation and the time of model maturation were observed. After the model, the model group, the traditional Chinese medicine group, the western medicine group, the blank group and the sham operation group were randomly divided into two groups: the first day, the third day and the fifth day after the model operation. The treatment, model group, blank group and sham-operation group were given to the same amount of normal saline for the treatment of treatment, model group, blank group and sham-operation group. After 28 days of continuous administration, the expression of TGF-CD1 and Smad3 in the normal peritoneal tissue of the model rats and the normal peritoneal tissue of the blank group were detected by immunohistochemistry and RT-PCR. Results (1) Cyst volume: the cyst was significantly lower than that before treatment (P0.05), the right side cyst was significantly lower than that before treatment (P0.05), and there was no significant difference before and after the treatment of the left side cyst. (2) VAS dysmenorrhea: the degree of dysmenorrhea and the duration of the dysmenorrhea were gradually decreased and shortened with the prolongation of the period of the administration, and the degree of dysmenorrhea was significantly lower than that before the treatment (P0.01), and the effect on shortening the duration of the dysmenorrhea was relatively slow. The effect of the traditional Chinese medicine on the simple OEM group and the OEM combined adenomyosis group was relatively fast after four menstrual cycles. (3) The symptom of COX-dysmenorrhea: the severity and duration of COX symptom gradually decreased and shortened with the treatment period, among which, the pain of the small abdomen, the pain of the back (the waist and the waist), the weakness, the easy to cause the symptoms and the treatment before and after the treatment had a very significant difference (P0.01); the inappetence, the headache, the insomnia, There was a significant difference before and after the treatment of depression (P0.05). (4) CPP symptom: The clinical symptoms of CPP were gradually reduced with the time of taking the medicine, and the effect of the traditional Chinese medicine on the simple OEM group was better than that of the OEM combined adenomyosis group. There was no significant difference in the four menstrual cycles of the OEM combined with the adenomyosis. (5) Menstrual amount: the over-time period of the menstrual period is gradually reduced with the time of taking the medicine, and the mean value of the menstrual period after the six menstrual cycles is reduced to the normal range. (6) After five menstrual cycles, there was a significant difference between the five menstrual cycles and the treatment (P0.05). (7) CA125 and CA199: The effect of blood circulation and elimination on serum CA125 and CA199 is not ideal. (8) The rate of pregnancy: promoting blood circulation and eliminating the difference can promote the pregnancy of the OEM. (1) The model of the implantation of the endometrium on the intestinal mucosa is used to transplant the endometrium. The success rate of the model is 100%. The model of the most appropriate EM-pelvic adhesion rat model was studied in the 5-day-old rat model after molding. (2) The expression of TGF-CD1 and Smad3 in the adhesion-peritoneal tissue of the EM-pelvic adhesion rats was significantly higher than that in the sham-operated group (P0.01), and the expression of the Smad3 and the expression of the Smad3 gene and the expression of the protein in the group of the traditional Chinese medicine and the western medicine group was significantly lower than that in the model group (P0.01). but still higher than that in the sham operation group (P0.05). The lower the drug intervention of the traditional Chinese medicine group, the lower the adhesion score of the pelvic adhesion, the lower the expression of the TGF-1 gene and the protein, the difference between the groups (P0.05), the drug intervention time of the western medicine group and the TGF-1 1, Smad3 protein and gene expression did not show corresponding trend. Conclusion 1Clinical observation: To reduce the volume of the OEM, relieve the symptoms of pain (dysmenorrhea and CPP), to improve the menstrual situation, to promote the fertility, but to reduce the levels of CA125 and CA199 in the serum. In order to improve the adhesion of the EM, the more effective the intervention of the traditional Chinese medicine, the more the curative effect of pelvic adhesion is improved.
【学位授予单位】：中国中医科学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R271.9

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