SLE相关血栓性微血管病血管内皮—间充质转分化的研究

发布时间：2018-04-26 16:21

  本文选题：系统性红斑狼疮 + 血栓性微血管病　； 参考：《南京大学》2017年硕士论文

【摘要】：目的:研究系统性红斑狼疮相关血栓性微血管病(SLE-TMA)患者的TMA病变血管内皮细胞表型(CD31、VE-cadherin、α-SMA和TGF-β)的变化,以及表型变化与肾间质小动脉病变、肾间质纤维化程度及治疗反应之间的联系。方法:共有30名经过肾组织活检后明确为SLE-TMA的患者被纳入本研究。收集患者的一般临床资料、实验室检查资料以及肾组织活检标本资料,根据患者有TMA病变的肾血管的组织病理学表现将所有患者分为急性TMA和慢性TMA,取正常肾组织的间质小动脉为正常对照组。肾间质小动脉的内皮细胞采用分子标志物CD31和α-SMA的间接免疫荧光双重染色进行定位,并对肾组织进行CD31、VE-cadherin、α-SMA和TGF-β的免疫组织化学染色,采用Image Pro Plus 6.0对上述分子标志物的表达量进行定量分析,以平均光密度(MD,指积分光密度IOD/肾间质小动脉内皮层面积)表示各分子标志物的表达强度。运用计算机图像分析系统(Aperio Image Scope)测量SLF-TMA患者的肾组织间质纤维化的面积百分比。结果:肾组织分子标志物的间接免疫荧光双重染色结果显示SLE-TMA中TMA病变的间质小动脉内皮细胞表达α-SMA,而正常对照组小动脉内皮细胞不表达α-SMA。与正常对照组小动脉相比,急性TMA病变小动脉内皮细胞的CD31、VE-cadherin和TGF-β表达量明显降低(P0.05),而α-SMA的表达量显著升高(P0.01);与正常对照组相比,慢性TMA病变小动脉内皮细胞的CD31、VE-cadherin和TGF-β表达均明显降低(P0.01),而α-SMA表达较正常对照组明显升高(P0.01);与急性TMA病变小动脉相比,慢性TMA病变小动脉内皮细胞的 CD31(P=0.02)、VE-cadherin(P=0.058)和TGF-β(P0.01)表达均更低,而α-SMA表达较急性TMA组更高(P=0.09)。肾组织间质小动脉CD31的MD与肾组织间质的纤维化面积百分比呈负相关(r=-0.458,P=0.011),而α-SMA的MD与肾组织间质的纤维化面积百分比呈正相关(r=0.439,P=0.015)。α-SMA表达量是影响SLE-TMA患者近期治疗反应的危险因素。结论:SLE-TMA患者肾组织中发生TMA病变的间质小动脉中内皮细胞正常标记物如CD31、VE-cadherin的表达降低,α-SMA的表达升高,这些结果表明内皮细胞发生了向间充质细胞表型的转变,且分子标志物表达量的变化与血管病变进展相关;肾间质中TMA病变小动脉CD31表达水平的下降以及α-SMA表达水平的升高与肾组织的间质纤维化程度相关,并影响治疗反应。
[Abstract]:Objective: to study the changes of vascular endothelial cell phenotype (CD31, 伪 -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 伪 -SMA, and the renal tissues were stained by immunohistochemical staining of CD31 and VE-cadherin, 伪 -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 伪 -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 伪 -SMA increased significantly compared with the control group, and the expression of 伪 -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 伪 -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 伪 -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 伪 -SMA was positively correlated with the percentage of fibrosis area of renal interstitial tissue. 伪 -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 伪 -SMA in the interstitial arterioles with TMA lesions in the renal tissue of patients with TMA were decreased, and the expression of 伪 -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 伪 -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.
【学位授予单位】：南京大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R593.241;R692
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本文编号：1806763