【摘要】：目的：盆腔炎性疾病后遺癥(SPID)是女性常見病、多發(fā)病,是嚴重影響婦女健康的重要疾病之一,目前西醫(yī)尚無特效療法,治療較為棘手,中醫(yī)藥治療該病具有一定的特色和優(yōu)勢。中醫(yī)認為SPID以血瘀為病機核心,血瘀貫穿疾病發(fā)展始終。故本研究首次提出“血瘀微環(huán)境”的理念,并提出“化瘀通絡(luò)法”可改善“血瘀微環(huán)境”的假說。擬建立以祖國醫(yī)學(xué)整體思維模式與現(xiàn)代醫(yī)學(xué)相結(jié)合的評價體系,評價SPID盆腔內(nèi)血流動力學(xué)及血管生成水平,以及化瘀通絡(luò)中藥“丹枝飲”對“血瘀微環(huán)境”及血管新生水平的影響。方法：本課題以動物實驗和臨床實驗,全面而客觀地對“血瘀微環(huán)境”進行驗證,同時評價化瘀通絡(luò)法中藥“丹枝飲”對SPID的療效。動物實驗：以宮腔種植鼠衣原體法復(fù)制小鼠SPID模型。造模成功后,以“丹枝飲”連續(xù)治療SPID小鼠3個動情周期,通過觀察：(1)小鼠子宮動脈血流收縮期峰值(PSV)、卵巢動脈PSV,腸系膜微循環(huán)血流灌注量,盆壁微小血管血流灌注量,立體地分析SPID小鼠盆腔血流動力學(xué)情況及中藥的干預(yù)作用；(2)小鼠上生殖道組織(子宮、輸卵管、卵巢、結(jié)締組織)VEGF、Ang-2以及OPN的蛋白表達水平,評價SPID小鼠盆腔內(nèi)血管新生水平以及中藥對其表達的影響。臨床實驗：將就診于北京中醫(yī)藥大學(xué)東方醫(yī)院SPID寒凝血瘀證患者隨機分為觀察組和對照組。觀察組予丹枝飲,對照組予臨床常用方劑——桂枝茯苓丸,分別治療3個月經(jīng)周期,比較兩組盆腔血流動力學(xué)指標(biāo)、VAS評分、局部體征評分及中醫(yī)證候評分以評價化瘀通絡(luò)法對盆腔“血瘀微環(huán)境”的影響及對SPID的臨床療效。結(jié)果：(1)SPID小鼠盆腔血流動力學(xué)較正常小鼠明顯降低,經(jīng)中藥干預(yù)后血流動力學(xué)指標(biāo)明顯改善,盆腔疼痛隨之減輕,且中劑量中藥效果總體優(yōu)于大劑量、小劑量中藥；(2)SPID盆腔血液流速與慢性盆腔痛疼痛程度呈明顯負相關(guān)；(3)SPID小鼠上生殖道組織VEGF、Ang-2、OPN表達較正常小鼠顯著增高,經(jīng)中藥干預(yù)后,各種因子表達均下降,以大劑量、中劑量下調(diào)作用顯著；(4)SPID寒凝血瘀證患者治療前后盆腔血流動力學(xué)指標(biāo)有顯著差異,VAS評分、局部體征評分及中醫(yī)證候評分均顯著下降,丹枝飲效果總體優(yōu)于桂枝茯苓丸。結(jié)論：經(jīng)過動物實驗及臨床實驗,得出以下結(jié)論：(1)SPID病患盆腔內(nèi)處于“血瘀微環(huán)境”狀態(tài)；(2)SPID盆腔內(nèi)血流速度與慢性盆腔痛呈負相關(guān)；(3)SPID小鼠上生殖道組織VEGF、Ang-2、OPN高表達,提示病變局部血管新生水平較高；(4)化瘀通絡(luò)法可以改善盆腔血流動力學(xué),緩解盆腔“血瘀微環(huán)境”狀態(tài)；(5)化瘀通絡(luò)法可降低SPID小鼠上生殖道血管新生水平,有利于組織修復(fù),避免進一步破壞；(6)化瘀通絡(luò)法可明顯改善SPID患者慢性盆腔痛、局部體征和中醫(yī)證候,療效顯著。
[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.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R271.9

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