本文選題：IgA腎病 + 甘露糖結(jié)合凝集素�。� 參考：《重慶醫(yī)科大學(xué)》2011年碩士論文

【摘要】：目的 補(bǔ)體具有多種生物學(xué)功能,廣泛參與機(jī)體抗微生物防御反應(yīng)以及免疫調(diào)節(jié),另一方面也造成免疫病理損傷。隨著補(bǔ)體研究的不斷深入,膜攻擊復(fù)合物在多種腎臟疾病的組織和尿液中檢出,甚至發(fā)現(xiàn)系膜細(xì)胞增生具有補(bǔ)體依賴性。系膜區(qū)沉積的IgA可能通過活化補(bǔ)體來激活人系膜細(xì)胞(HMC)、導(dǎo)致IgA腎病(IgAN)腎小球損傷的機(jī)制受到越來越多的關(guān)注。本研究旨在明確MBL在IgAN發(fā)病中的作用,探討甘露糖結(jié)合凝集素(MBL)、MBL絲氨酸蛋白酶(MASP-1)沉積與兒童IgAN臨床表現(xiàn)、病理改變的關(guān)系,進(jìn)一步探討局部沉積的MBL來源,為臨床有效的治療提供實(shí)驗(yàn)依據(jù)。 方法 1用ELISA方法檢測(cè)20例IgAN患兒和正常兒童血清的MBL水平,免疫組化檢測(cè)53例IgA腎病、23例非IgA沉積腎小球疾病患兒腎組織甘露聚糖結(jié)合凝集素(MBL)、MBL相關(guān)的絲氨酸蛋白酶-1(MASP-1)、C3、C1q、IgA和C5b-9的表達(dá),了解有無MBL- MASP-12途徑補(bǔ)體活化參與IgAN發(fā)病. 2.回顧性分析MBL-MASP-1沉積陽性組和MBL-MASP-1沉積陰性組患兒不同臨床表現(xiàn)的差異;分析IgAN的MBL沉積強(qiáng)度與病理分級(jí)的相關(guān)性,了解不同程度補(bǔ)體活化與IgAN病理損害的關(guān)系。 3.用含有IgA腎病病人血清體外培養(yǎng)人系膜細(xì)胞(HMC),隨機(jī)分為0小時(shí)、6小時(shí)、12小時(shí)和24小時(shí)組,取上清液,用ELISA方法檢測(cè)各組細(xì)胞上清液甘露糖結(jié)合凝集素(MBL)水平和RT-PCR方法檢測(cè)細(xì)胞MBLmRNA表達(dá),了解系膜細(xì)胞在凝集素途徑補(bǔ)體活化中的作用。 結(jié)果 1.1第一部分補(bǔ)體活化的凝集素途徑在IgAN發(fā)病中作用 1.22例IgAN患兒腎小球有MBL、MASP-1、C3和C5b-9沉積, 23例非IgA沉積腎臟疾病患兒均無MBL和MASP-1沉積;系膜區(qū)MBL沉積強(qiáng)度與IgA沉積強(qiáng)度之間存在正相關(guān)關(guān)系(rs=0.865),但與IgAN病理分級(jí)無關(guān); 2.IgA腎病患兒血清MBL水平和對(duì)照組統(tǒng)計(jì)學(xué)無明顯的差異。 3.MBL-MASP沉積陽性組患兒蛋白尿水平顯著高于MBL-MASP沉積陰性組,肉眼血尿更為多見。 1.2第二部分系膜細(xì)胞對(duì)補(bǔ)體活化的凝集素途徑在IgA腎病發(fā)病作用中的影響 1.四組細(xì)胞上清液比較,0-12小時(shí)MBL水平降低,統(tǒng)計(jì)學(xué)有差異(p=0.003);12-24小時(shí)MBL水平升高,統(tǒng)計(jì)學(xué)有差異(p0.001)。 2.與IgA腎病患兒血清共培養(yǎng)24小時(shí)后HMC,HMC的MBL檢測(cè)證實(shí)了MBLmRNA表達(dá)。 結(jié)論 1.局部凝集素途徑的補(bǔ)體活化在IgAN發(fā)病中有重要作用。 2.系膜細(xì)胞能表達(dá)MBL,可能在導(dǎo)致IgA腎病發(fā)病的局部凝集素途徑補(bǔ)體活化中發(fā)揮作用。
[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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R392

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