补体活化的凝激素途径在IgAN发病中的作用及机制探讨

发布时间：2018-05-31 07:38

  本文选题：IgA肾病 + 甘露糖结合凝集素　； 参考：《重庆医科大学》2011年硕士论文

【摘要】：目的 补体具有多种生物学功能,广泛参与机体抗微生物防御反应以及免疫调节,另一方面也造成免疫病理损伤。随着补体研究的不断深入,膜攻击复合物在多种肾脏疾病的组织和尿液中检出,甚至发现系膜细胞增生具有补体依赖性。系膜区沉积的IgA可能通过活化补体来激活人系膜细胞(HMC)、导致IgA肾病(IgAN)肾小球损伤的机制受到越来越多的关注。本研究旨在明确MBL在IgAN发病中的作用,探讨甘露糖结合凝集素(MBL)、MBL丝氨酸蛋白酶(MASP-1)沉积与儿童IgAN临床表现、病理改变的关系,进一步探讨局部沉积的MBL来源,为临床有效的治疗提供实验依据。 方法 1用ELISA方法检测20例IgAN患儿和正常儿童血清的MBL水平,免疫组化检测53例IgA肾病、23例非IgA沉积肾小球疾病患儿肾组织甘露聚糖结合凝集素(MBL)、MBL相关的丝氨酸蛋白酶-1(MASP-1)、C3、C1q、IgA和C5b-9的表达,了解有无MBL- MASP-12途径补体活化参与IgAN发病. 2.回顾性分析MBL-MASP-1沉积阳性组和MBL-MASP-1沉积阴性组患儿不同临床表现的差异;分析IgAN的MBL沉积强度与病理分级的相关性,了解不同程度补体活化与IgAN病理损害的关系。 3.用含有IgA肾病病人血清体外培养人系膜细胞(HMC),随机分为0小时、6小时、12小时和24小时组,取上清液,用ELISA方法检测各组细胞上清液甘露糖结合凝集素(MBL)水平和RT-PCR方法检测细胞MBLmRNA表达,了解系膜细胞在凝集素途径补体活化中的作用。 结果 1.1第一部分补体活化的凝集素途径在IgAN发病中作用 1.22例IgAN患儿肾小球有MBL、MASP-1、C3和C5b-9沉积, 23例非IgA沉积肾脏疾病患儿均无MBL和MASP-1沉积;系膜区MBL沉积强度与IgA沉积强度之间存在正相关关系(rs=0.865),但与IgAN病理分级无关; 2.IgA肾病患儿血清MBL水平和对照组统计学无明显的差异。 3.MBL-MASP沉积阳性组患儿蛋白尿水平显著高于MBL-MASP沉积阴性组,肉眼血尿更为多见。 1.2第二部分系膜细胞对补体活化的凝集素途径在IgA肾病发病作用中的影响 1.四组细胞上清液比较,0-12小时MBL水平降低,统计学有差异(p=0.003);12-24小时MBL水平升高,统计学有差异(p0.001)。 2.与IgA肾病患儿血清共培养24小时后HMC,HMC的MBL检测证实了MBLmRNA表达。 结论 1.局部凝集素途径的补体活化在IgAN发病中有重要作用。 2.系膜细胞能表达MBL,可能在导致IgA肾病发病的局部凝集素途径补体活化中发挥作用。
[Abstract]:objective
Complement has a variety of biological functions, widely involved in the body's anti microbial defense response and immune regulation, on the other hand, it also causes immune pathological damage. With the development of complement research, membrane attack complex is detected in the tissues and urine of various renal diseases, and even the proliferation of the mesangial cells is dependent on the complement. IgA may be activated by activated complement to activate human mesangial cells (HMC), leading to more and more attention in the mechanism of IgA nephropathy (IgAN) glomerular damage. This study aims to identify the role of MBL in the pathogenesis of IgAN, to explore the clinical manifestations and pathological changes of mannose binding lectin (MBL), MBL serine protease (MASP-1) and IgAN in children. To further explore the sources of MBL in local deposition, and to provide experimental evidence for clinical effective treatment.
Method
1 ELISA was used to detect the level of serum MBL in 20 children with IgAN and normal children. 53 cases of IgA nephropathy were detected by immunohistochemistry, 23 cases of non IgA deposition glomerular disease renal tissue mannan binding lectin (MBL), MBL related serine proteinase -1 (MASP-1), C3, C1q, IgA, and expressions. With IgAN.
2. the differences in different clinical manifestations of children with MBL-MASP-1 deposition positive group and MBL-MASP-1 negative group were analyzed retrospectively. The correlation between MBL deposition intensity and pathological classification of IgAN was analyzed, and the relationship between different degree of complement activation and pathological lesion of IgAN was analyzed.
3. the human mesangial cells (HMC) were cultured in vitro with the serum of patients with IgA nephropathy. They were randomly divided into 0 hours, 6 hours, 12 hours and 24 hours. The supernatant was taken. The level of mannose binding lectin (MBL) in the supernatant of each group was detected by ELISA and the expression of MBLmRNA in the cell was detected by RT-PCR. The role.
Result
1.1 Part 1 the role of complement activated lectin pathway in the pathogenesis of IgAN
The glomeruli of 1.22 children with IgAN had MBL, MASP-1, C3 and C5b-9 deposition. There was no MBL and MASP-1 deposition in 23 children with non IgA deposition of kidney disease, and there was a positive correlation between MBL deposition intensity and IgA deposition intensity in the mesangial region, but it was not related to the pathologic grading of IgAN.
There was no significant difference in serum MBL level between 2.IgA nephropathy group and control group.
The level of proteinuria in 3.MBL-MASP positive group was significantly higher than that in MBL-MASP negative group, and gross hematuria was more common.
1.2 second part of the role of lectin pathway on complement activation in mesangial cells in the pathogenesis of IgA nephropathy
1. compared with the four groups of cell supernatants, the level of MBL decreased at 0-12 hours, the difference was statistically significant (p=0.003), and the level of MBL increased 12-24 hours (p0.001).
2. after 24 hours of co culture with children with IgA nephropathy, MBL expression of HMC and HMC confirmed MBLmRNA expression.
conclusion
1. complement activation of local lectin pathway plays an important role in the pathogenesis of IgAN.
2. mesangial cells can express MBL, which may play a role in complement activation of local lectin pathway in the pathogenesis of IgA nephropathy.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R392

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