本文選題：系統(tǒng)性紅斑狼瘡 + 血栓性微血管病��； 參考：《南京大學》2017年碩士論文

【摘要】：目的:研究系統(tǒng)性紅斑狼瘡相關(guān)血栓性微血管病(SLE-TMA)患者的TMA病變血管內(nèi)皮細胞表型(CD31、VE-cadherin、α-SMA和TGF-β)的變化,以及表型變化與腎間質(zhì)小動脈病變、腎間質(zhì)纖維化程度及治療反應之間的聯(lián)系。方法:共有30名經(jīng)過腎組織活檢后明確為SLE-TMA的患者被納入本研究。收集患者的一般臨床資料、實驗室檢查資料以及腎組織活檢標本資料,根據(jù)患者有TMA病變的腎血管的組織病理學表現(xiàn)將所有患者分為急性TMA和慢性TMA,取正常腎組織的間質(zhì)小動脈為正常對照組。腎間質(zhì)小動脈的內(nèi)皮細胞采用分子標志物CD31和α-SMA的間接免疫熒光雙重染色進行定位,并對腎組織進行CD31、VE-cadherin、α-SMA和TGF-β的免疫組織化學染色,采用Image Pro Plus 6.0對上述分子標志物的表達量進行定量分析,以平均光密度(MD,指積分光密度IOD/腎間質(zhì)小動脈內(nèi)皮層面積)表示各分子標志物的表達強度。運用計算機圖像分析系統(tǒng)(Aperio Image Scope)測量SLF-TMA患者的腎組織間質(zhì)纖維化的面積百分比。結(jié)果:腎組織分子標志物的間接免疫熒光雙重染色結(jié)果顯示SLE-TMA中TMA病變的間質(zhì)小動脈內(nèi)皮細胞表達α-SMA,而正常對照組小動脈內(nèi)皮細胞不表達α-SMA。與正常對照組小動脈相比,急性TMA病變小動脈內(nèi)皮細胞的CD31、VE-cadherin和TGF-β表達量明顯降低(P0.05),而α-SMA的表達量顯著升高(P0.01);與正常對照組相比,慢性TMA病變小動脈內(nèi)皮細胞的CD31、VE-cadherin和TGF-β表達均明顯降低(P0.01),而α-SMA表達較正常對照組明顯升高(P0.01);與急性TMA病變小動脈相比,慢性TMA病變小動脈內(nèi)皮細胞的 CD31(P=0.02)、VE-cadherin(P=0.058)和TGF-β(P0.01)表達均更低,而α-SMA表達較急性TMA組更高(P=0.09)。腎組織間質(zhì)小動脈CD31的MD與腎組織間質(zhì)的纖維化面積百分比呈負相關(guān)(r=-0.458,P=0.011),而α-SMA的MD與腎組織間質(zhì)的纖維化面積百分比呈正相關(guān)(r=0.439,P=0.015)。α-SMA表達量是影響SLE-TMA患者近期治療反應的危險因素。結(jié)論:SLE-TMA患者腎組織中發(fā)生TMA病變的間質(zhì)小動脈中內(nèi)皮細胞正常標記物如CD31、VE-cadherin的表達降低,α-SMA的表達升高,這些結(jié)果表明內(nèi)皮細胞發(fā)生了向間充質(zhì)細胞表型的轉(zhuǎn)變,且分子標志物表達量的變化與血管病變進展相關(guān);腎間質(zhì)中TMA病變小動脈CD31表達水平的下降以及α-SMA表達水平的升高與腎組織的間質(zhì)纖維化程度相關(guān),并影響治療反應。
[Abstract]:Objective: to study the changes of vascular endothelial cell phenotype (CD31, 偽 -SMA and TGF- 尾) in patients with systemic lupus erythematosus associated thrombotic microangiopathy (SLE-TMA), and the relationship between phenotype and renal interstitial arteriopathy. The relationship between the degree of renal interstitial fibrosis and therapeutic response. Methods: a total of 30 patients identified as SLE-TMA after renal biopsy were included in this study. Collect the general clinical data, laboratory data and renal biopsy data of the patients, According to the histopathological findings of renal vessels with TMA lesion, all patients were divided into acute TMA and chronic TMA. The interstitial arterioles of normal renal tissue were taken as the normal control group. The endothelial cells of renal interstitial arterioles were located by indirect immunofluorescence double staining of molecular markers CD31 and 偽 -SMA, and the renal tissues were stained by immunohistochemical staining of CD31 and VE-cadherin, 偽 -SMA and TGF- 尾. Image Pro Plus 6.0 was used to quantitatively analyze the expression of the above molecular markers. The expression intensity of the molecular markers was expressed by the mean optical density (MDD) and the area of endothelium of the renal interstitial artery (IOD/). The area percentage of renal interstitial fibrosis in patients with SLF-TMA was measured by computer image analysis system (Aperio Image scope). Results: the results of indirect immunofluorescence double staining showed that 偽 -SMA was expressed in the endothelial cells of interstitial arterioles of TMA lesion in SLE-TMA, but not in the normal control group. Compared with the control group, the expression of CD31VE-cadherin and TGF- 尾 in the endothelial cells of the arterioles of acute TMA lesions decreased significantly, while the expression of 偽 -SMA increased significantly compared with the control group, and the expression of 偽 -SMA was significantly higher than that of the normal control group. The expression of CD31, VE-cadherin and TGF- 尾 in endothelial cells of arteriolar artery of chronic TMA was significantly lower than that of control group, while the expression of 偽 -SMA was significantly higher than that of normal controls, and the expression of CD31, P0. 02, VE-cadherin P0. 058) and TGF- 尾 P0. 01) in endothelial cells of arterioles of chronic TMA lesions were lower than those of acute arterioles of TMA. The expression of 偽 -SMA in acute TMA group was higher than that in acute TMA group. There was a negative correlation between MD of renal interstitial arterioles CD31 and the percentage of fibrosis area of renal interstitial tissue. The MD of 偽 -SMA was positively correlated with the percentage of fibrosis area of renal interstitial tissue. 偽 -SMA expression was a risk factor affecting the short-term therapeutic response of SLE-TMA patients. Conclusion the expression of normal endothelial cell markers, such as CD31, VE-cadherin, and the expression of 偽 -SMA in the interstitial arterioles with TMA lesions in the renal tissue of patients with TMA were decreased, and the expression of 偽 -SMA was increased. These results suggest that the endothelial cells have changed into the mesenchymal cells phenotype. The decrease of CD31 expression in arterioles of renal interstitial lesions and the increase of 偽 -SMA expression were correlated with the degree of interstitial fibrosis in renal tissues and the therapeutic response was affected by the changes of expression of molecular markers.
【學位授予單位】：南京大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R593.241;R692
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本文編號：1806763