化瘀通络法对盆腔炎性疾病后遗症盆腔血瘀微环境血流动力学及血管新生水平的影响

发布时间：2019-04-25 14:19

【摘要】：目的：盆腔炎性疾病后遗症(SPID)是女性常见病、多发病,是严重影响妇女健康的重要疾病之一,目前西医尚无特效疗法,治疗较为棘手,中医药治疗该病具有一定的特色和优势。中医认为SPID以血瘀为病机核心,血瘀贯穿疾病发展始终。故本研究首次提出“血瘀微环境”的理念,并提出“化瘀通络法”可改善“血瘀微环境”的假说。拟建立以祖国医学整体思维模式与现代医学相结合的评价体系,评价SPID盆腔内血流动力学及血管生成水平,以及化瘀通络中药“丹枝饮”对“血瘀微环境”及血管新生水平的影响。方法：本课题以动物实验和临床实验,全面而客观地对“血瘀微环境”进行验证,同时评价化瘀通络法中药“丹枝饮”对SPID的疗效。动物实验：以宫腔种植鼠衣原体法复制小鼠SPID模型。造模成功后,以“丹枝饮”连续治疗SPID小鼠3个动情周期,通过观察：(1)小鼠子宫动脉血流收缩期峰值(PSV)、卵巢动脉PSV,肠系膜微循环血流灌注量,盆壁微小血管血流灌注量,立体地分析SPID小鼠盆腔血流动力学情况及中药的干预作用；(2)小鼠上生殖道组织(子宫、输卵管、卵巢、结缔组织)VEGF、Ang-2以及OPN的蛋白表达水平,评价SPID小鼠盆腔内血管新生水平以及中药对其表达的影响。临床实验：将就诊于北京中医药大学东方医院SPID寒凝血瘀证患者随机分为观察组和对照组。观察组予丹枝饮,对照组予临床常用方剂——桂枝茯苓丸,分别治疗3个月经周期,比较两组盆腔血流动力学指标、VAS评分、局部体征评分及中医证候评分以评价化瘀通络法对盆腔“血瘀微环境”的影响及对SPID的临床疗效。结果：(1)SPID小鼠盆腔血流动力学较正常小鼠明显降低,经中药干预后血流动力学指标明显改善,盆腔疼痛随之减轻,且中剂量中药效果总体优于大剂量、小剂量中药；(2)SPID盆腔血液流速与慢性盆腔痛疼痛程度呈明显负相关；(3)SPID小鼠上生殖道组织VEGF、Ang-2、OPN表达较正常小鼠显著增高,经中药干预后,各种因子表达均下降,以大剂量、中剂量下调作用显著；(4)SPID寒凝血瘀证患者治疗前后盆腔血流动力学指标有显著差异,VAS评分、局部体征评分及中医证候评分均显著下降,丹枝饮效果总体优于桂枝茯苓丸。结论：经过动物实验及临床实验,得出以下结论：(1)SPID病患盆腔内处于“血瘀微环境”状态；(2)SPID盆腔内血流速度与慢性盆腔痛呈负相关；(3)SPID小鼠上生殖道组织VEGF、Ang-2、OPN高表达,提示病变局部血管新生水平较高；(4)化瘀通络法可以改善盆腔血流动力学,缓解盆腔“血瘀微环境”状态；(5)化瘀通络法可降低SPID小鼠上生殖道血管新生水平,有利于组织修复,避免进一步破坏；(6)化瘀通络法可明显改善SPID患者慢性盆腔痛、局部体征和中医证候,疗效显著。
[Abstract]:Objective: pelvic inflammatory sequelae (SPID) is a common and frequently occurring disease in women, and it is one of the important diseases that seriously affect women's health. At present, there is no special effect therapy in western medicine, and the treatment is difficult. Chinese medicine treatment of this disease has certain characteristics and advantages. Traditional Chinese Medicine (TCM) believes that blood stasis is the core of the pathogenesis of SPID, and blood stasis runs through the development of the disease. Therefore, this study put forward for the first time the idea of "blood stasis microenvironment", and put forward the hypothesis that "removing blood stasis and clearing collateral" can improve the "blood stasis micro environment". To establish an evaluation system based on the integrated thinking mode of Chinese medicine and modern medicine to evaluate the hemodynamic and angiogenic levels in the pelvis of SPID. And the effect of "Danzhi Yin" on blood stasis microenvironment and angiogenesis level of Huayu Tongluo herbal medicine. Methods: in this study, animal and clinical experiments were used to verify the microenvironment of blood stasis and evaluate the curative effect of "Danzhi Yin", a traditional Chinese medicine for removing blood stasis and clearing collaterals, on SPID. Animal experiment: the SPID model of mice was established by implantation of rodent cloak in uterine cavity. After successful establishment of the model, SPID mice were treated with Danzhi Yin continuously for three estrus cycles. (1) the PSV, mesenteric microcirculation perfusion volume of the uterine artery systolic peak (PSV), ovarian artery PSV, in mice was observed. The effect of traditional Chinese medicine (TCM) on pelvic hemodynamics in SPID mice was analyzed in three-dimensional analysis of the amount of blood flow of microvessels in pelvic wall. (2) the protein expression levels of VEGF,Ang-2 and OPN in the upper genital tract (uterus, oviduct, ovary, connective tissue) of mice were evaluated to evaluate the angiogenesis level in the pelvic cavity of SPID mice and the effect of traditional Chinese medicine on the expression. Clinical experiment: the patients with SPID syndrome of cold coagulation and blood stasis were randomly divided into observation group and control group in Oriental Hospital of Beijing University of traditional Chinese Medicine. The observation group was given Danzhi Yin, and the control group was given Guizhi Fuling Pill, which was commonly used in clinic, for 3 menstrual cycles respectively. The pelvic hemodynamic indexes and VAS score were compared between the two groups. Local sign score and TCM syndrome score were used to evaluate the effect of Huayu Tongluo method on pelvic "blood stasis microenvironment" and its clinical effect on SPID. Results: (1) the pelvic hemodynamics of SPID mice was significantly lower than that of normal mice. The hemodynamic indexes were improved obviously after the intervention of traditional Chinese medicine, and the pelvic pain was alleviated. The effect of middle-dose Chinese medicine was better than that of large-dose and low-dose traditional Chinese medicine as a whole. (2) the pelvic blood flow velocity of SPID was negatively correlated with the pain degree of chronic pelvic pain. (3) the expression of VEGF,Ang-2,OPN in the upper genital tract of SPID mice was significantly higher than that of normal mice. After intervention with traditional Chinese medicine, the expression of all kinds of factors decreased, especially in high dose and middle dose. (4) there was significant difference in pelvic hemodynamic index before and after treatment in SPID patients with cold coagulation and blood stasis syndrome. The VAS score, local sign score and TCM syndrome score were significantly decreased, and the effect of Danzhi Yin was superior to Guizhi Fuling Pill in general. Conclusion: through animal and clinical experiments, the following conclusions can be drawn: (1) SPID patients are in the state of "blood stasis microenvironment" in the pelvis, (2) the velocity of blood flow in the pelvic cavity of SPID is negatively correlated with chronic pelvic pain; (3) the high expression of VEGF,Ang-2,OPN in the upper genital tract of SPID mice suggested a higher level of angiogenesis in the lesion area, (4) Huayu Tongluo method could improve the pelvic hemodynamics and alleviate the "blood stasis microenvironment" in the pelvis. (5) Huayu Tongluo method can reduce the level of angiogenesis in the upper genital tract of SPID mice, which is beneficial to tissue repair and avoid further destruction. (6) Huayu Tongluo method can obviously improve chronic pelvic pain, local signs and TCM syndrome in patients with SPID.
【学位授予单位】：北京中医药大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R271.9

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