本文選題：系統(tǒng)性硬化 + 肺動脈高壓��； 參考：《南昌大學》2017年碩士論文

【摘要】：背景和目的:肺動脈高壓(pulmonary arterial hypertension,PAH)是一類病因復雜、預后較差的疾病。特別是結(jié)締組織病(connective tissue disease,CTD)相關PAH,其起病隱匿,診斷不充分,在臨床診療中仍是難點。微循環(huán)障礙是系統(tǒng)性硬化(systemic sclerosis,SSc)發(fā)病機制中的中心環(huán)節(jié),兩者間的相關性也越來越被認可。由于臨床研究的眾多局限,動物模型對疾病發(fā)病機制及診療手段的探索提供了極大的幫助。本研究擬用博來霉素(bleomycin,BLM)聯(lián)合野百合堿(monocrotaline,MCT)誘導模擬SSc合并PAH發(fā)病機制的兔模型,探討球結(jié)膜微循環(huán)與PAH的聯(lián)系,及其在疾病中的早期預測價值。同時,血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)既往已被多個研究證實在微循環(huán)障礙、血管重塑中發(fā)揮重要作用。本文試圖在動物模型中,對PAH、球結(jié)膜微循環(huán)分析及VEGF水平的相關性進行討論,進一步探索球結(jié)膜微循環(huán)在SSc合并PAH中的意義。方法:1.選取新西蘭雄兔24只,隨機分為三組(溶劑對照組、模型組、激素組),每組8只。模型組及激素組分別一次性腹腔注射1%的MCT50mg/kg及每日腹部皮下注射BLM 100ul(濃度1mg/ml),激素組同時每日腹腔注射甲潑尼龍(methylprednisolone,MP)2.6mg/kg(濃度1mg/ml),三周后停止給藥。隨后,利用右心導管測量平均肺動脈壓(mean pulmonary arterial pressure,mPAP),與溶劑對照組對比,判斷造模是否成功。并通過測量右心室肥大指數(shù)(right ventricular hypertrophy index,RVHI)及完善組織病理,進一步評估模型是否符合SSc合并PAH病理特點。2.給藥前后進行球結(jié)膜微循環(huán)分析,利用酶聯(lián)免疫吸附法(ELISA)檢測血清VEGF表達。分析球結(jié)膜微循環(huán)積分、VEGF濃度及mPAP的相關性,并利用ROC曲線判斷球結(jié)膜微循環(huán)積分對SSc合并PAH的診斷價值。結(jié)果:1.模型組mPAP及RVHI均顯著高于溶劑對照組和激素組,有統(tǒng)計學意義(P0.05)。2.組織病理:皮膚染色顯示,模型組皮損處表皮萎縮并角化過度,真皮層出現(xiàn)少量淋巴細胞、漿細胞浸潤;肺組織染色顯示,模型組肺泡內(nèi)可見大量出血,細小動脈肌化并不規(guī)則增厚,形成叢樣結(jié)構(gòu),伴有淋巴細胞、漿細胞浸潤。3.結(jié)膜微循環(huán)分析顯示,模型組總積分較其他兩組有明顯差異(P0.05),主要表現(xiàn)在血管增粗、血管扭曲、網(wǎng)狀畸形、出血、血管色調(diào)等方面,以上項目均與mPAP成正相關(P0.05)。4.球結(jié)膜微循環(huán)總積分ROC曲線分析,曲線下面積為0.852(P0.05)�？偡�5.2分對應的正確診斷指數(shù)最大,把球結(jié)膜微循環(huán)總積分≥5.2分作為輔助診斷PAH的分界點,其敏感度為88.9%,特異度為75.0%。5.模型組血清VEGF濃度較其他兩組有顯著差異(P0.05),并與球結(jié)膜微循環(huán)總積分及mPAP成正相關(P0.05)。結(jié)論:1.新西蘭雄兔利用BLM聯(lián)合MC T注射可以成功模擬SSc合并PAH模型。2.SSc合并PAH存在球結(jié)膜微循環(huán)障礙,其嚴重程度與mPAP成正相關,特別是在血管增粗、血管扭曲、出血、網(wǎng)狀畸形、血管色調(diào)等方面。3.球結(jié)膜微循環(huán)總積分≥5.2分可以作為輔助診斷PAH的分界點,其敏感度為88.9%,特異度為75.0%。4.SSc合并PAH中血清VEGF水平有所升高,并與球結(jié)膜微循環(huán)總分、mPAP有一定的相關性。
[Abstract]:Background and purpose: pulmonary arterial hypertension (PAH) is a kind of disease with complex causes and poor prognosis. Especially the connective tissue disease (CTD) related PAH, its onset is hidden, and the diagnosis is not sufficient. It is still difficult in clinical diagnosis and treatment. Microcirculation disorder is systemic sclerosis (systemic sclerosis, SSc). The central link in the pathogenesis is becoming more and more recognized. Because of the numerous limitations of the clinical research, animal models provide great help to the pathogenesis and the exploration of the means of diagnosis and treatment. This study is to use bleomycin (BLM) combined with monocrotaline (MCT) to induce simulated SSc and the pathogenesis of PAH. The rabbit model of the mechanism is used to explore the relationship between the microcirculation of conjunctiva and PAH, and its early prediction value in the disease. At the same time, vascular endothelial growth factor (VEGF) has been proved to play an important role in microcirculation disturbance and vascular remodeling. This article tries to be in the animal model, PAH, nodal The significance of the membrane microcirculation analysis and the correlation of VEGF level was discussed, and the significance of the spherical conjunctival microcirculation in the SSc combined with PAH was further explored. Methods 1. New Zealand male rabbits were selected and divided into three groups randomly (solvent control group, model group, hormone group), with 8 rats in each group. The model group and hormone group were injected into the abdomen of 1% MCT50mg/kg and daily abdomen respectively. BLM 100ul (concentration of 1mg/ml) was injected subcutaneously, and the hormone group was intraperitoneally injected with methylprednisolone (methylprednisolone, MP) 2.6mg/kg (concentration 1mg/ml) and stopped given three weeks later. Then, the mean pulmonary arterial pressure (mean pulmonary arterial pressure, mPAP) was measured by the right cardiac catheterization, and compared with the solvent control group, the success of the model was judged and passed. The right ventricular hypertrophy index (right ventricular hypertrophy index, RVHI) and the histopathology were perfected to further assess whether the model was consistent with the SSc combined with the pathological features of PAH to analyze the microcirculation of nodular conjunctiva before and after the administration of.2., and the expression of serum VEGF was detected by enzyme linked immunosorbent assay (ELISA). The microcirculation integral of the conjunctiva, VEGF concentration and mPAP were analyzed. The value of the ROC curve was used to determine the value of the microcirculation integral of the bulbar conjunctiva to the diagnosis of SSc combined with PAH. Results: 1. model group mPAP and RVHI were significantly higher than that of the solvent control group and the hormone group. There was a statistically significant (P0.05).2. histopathology: skin staining showed that the epidermis of the skin lesions of the model group was atrophied and hyperkeratosis, and the dermis appeared a small amount of lymph. Cells, plasma cells infiltration, lung tissue staining showed that a large number of bleeding in the alveoli of the model group, small artery myochemical thickening, forming a plexus like structure, accompanied by lymphocyte, plasma cell infiltration.3. conjunctiva microcirculation analysis showed that the total integral of the model group was significantly different from the other two groups (P0.05), mainly manifested in vascular thickening, vascular distortion. In the aspects of reticular malformation, bleeding and blood vessel hue, all the above items were analyzed with the total integral ROC curve of mPAP (P0.05).4. spherical conjunctiva microcirculation. The area under the curve was 0.852 (P0.05). The total score of 5.2 points was the largest, and the total score of the microcirculation of the conjunctiva was more than 5.2 as the demarcation point of the auxiliary diagnostic PAH, and its sensitivity was 88.9. The concentration of serum VEGF in the 75.0%.5. model group was significantly different from that of the other two groups (P0.05), and it was positively correlated with the total integral integral of the conjunctival microcirculation and mPAP (P0.05). Conclusion: 1. the use of BLM combined with MC T injection in New Zealand male rabbits can successfully simulate SSc combined PAH model.2.SSc conjunctival PAH exists the ball conjunctival microcirculation disorder, its severity is There was a positive correlation, especially in vascular thickening, vascular distortion, bleeding, reticular malformation, and blood vessel hue, the total integral of the.3. conjunctiva microcirculation was more than 5.2 points, which could be used as a demarcation point for the diagnosis of PAH, and its sensitivity was 88.9%. The specificity of the degree of specificity was that the serum level of VEGF in the 75.0%.4.SSc combined with PAH increased, and the total score of the conjunctival microcirculation of the ball and mPAP had one. Definite correlation.
【學位授予單位】：南昌大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R593.25;R544.1

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