特发性膜性肾病患者早期肠道菌群及SIgA的检测及其意义

发布时间：2018-05-08 13:40

本文选题：膜性肾病 + 特发性　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:膜性肾病(membranous nephropathy,MN)是引起成人肾病综合征最常见的病因,其病理学特征为肾小球基底膜外脏层上皮细胞下免疫复合物的沉积伴肾小球基底膜弥漫性增厚,病因不明者称为特发性膜性肾病(idiopathic membranous nephropathy,IMN)。有研究报道,我国IMN发病率占全部原发性肾小球疾病的9.54%,而且IMN的发生率呈逐年升高的趋势。目前MN的发病机制尚未完全阐明,因此进一步探究IMN的发病机制对于明确疾病诊断和指导临床治疗有着重要意义。肠道菌群、SIgA和肠粘膜通透性分别代表肠粘膜生物屏障、免疫屏障和机械屏障,肠粘膜屏障系统的异常可能参与了自身免疫性疾病的发生和发展。有研究发现MN患儿体内存在阳离子牛血清白蛋白(BSA),其在未分解时可能透过患儿未成熟的肠粘膜屏障吸收入血,导致MN的发生。IMN患者是否存在肠粘膜屏障损伤?肠粘膜损伤与IMN的发病关系如何?本研究通过检测肠道菌群数量和分泌型免疫球蛋白A(Secretory immunoglobulin A,SIgA)水平来评价肠粘膜生物屏障和免疫屏障,探讨其与IMN发病的关系,以期为IMN的临床治疗提供科学指导和理论依据。方法:选取2016年5月~2016年12月在河北医科大学第三医院肾内科住院,肾穿刺病理活检,并经免疫荧光、光镜和电镜证实为IMN的患者51例,作为病例组(IMN组),其中男性34人,女性17人,平均年龄46.57±12.88岁,平均BMI 25.30±3.52 kg/m2;选取同期来我院体检的健康人21例,作为正常对照组(健康对照组),其中男性13人,女性8人,平均年龄52.62±14.23岁,平均BMI 24.65±3.01kg/m2。所有IMN患者发病时间均在1个月内,入组前未应用激素及免疫抑制剂治疗。收集入组者清晨空腹第一次粪便标本。粪便中双歧杆菌与大肠杆菌数量之比(Bifidobacteria/E.coli,B/E)评价肠道微生态环境。和健康对照组相比,B/E值降低说明肠道菌群失调。1应用实时荧光定量PCR(real time-PCR,RT-PCR)技术检测粪便双歧杆菌、嗜酸乳杆菌、大肠杆菌(escherichiacoli,e.coli)和粪肠球菌的含量,评价肠粘膜生物屏障功能。计算b/e比值评价肠道微生态环境。2采用酶联免疫吸附测定法(enzyme-linkedimmunosorbentassay,elisa)检测粪便siga水平,评价肠粘膜免疫屏障功能。3对imn患者早期肠道菌群、siga、b/e值与血白蛋白、尿蛋白分别进行相关分析。对肠道菌群、b/e值与siga之间互相进行相关分析。采用spss21.0统计软件进行统计分析。采用均数±标准差(x±s)对正态分布的计量资料进行描述;采用中位数(最小值-最大值)对偏态分布的计量资料进行描述;两样本均数比较满足正态、方差齐时采用t检验;不满足时采用mann-whitneyu检验;相关分析满足双变量正态分布时采用perason直线相关分析,不满足时采用spearman秩相关分析。p0.05时差异有统计学意义。结果:1imn组与健康对照组相比粪便双歧杆菌、嗜酸乳杆菌、粪肠球菌数量和b/e值均下降,大肠杆菌数量增加,但差异均无统计学意义(p0.05)。2imn组与健康对照组相比粪便siga表达量明显下降,p0.05,差异有统计学意义。3粪便双歧杆菌、嗜酸乳杆菌、大肠杆菌、粪肠球菌及b/e值与血白蛋白、尿蛋白均无相关性(p0.05)。siga与血白蛋白、尿蛋白均无相关性(p0.05)。大肠杆菌与siga呈负相关,r=-0.344,p=0.0130.05;b/e值与siga呈正相关,r=0.382,p=0.0060.05。结论:1肠道菌群在imn早期没有异常变化,前者与imn是否直接相关有待进一步研究。2结果显示肠道菌群中大肠杆菌与siga相关,后者在imn中有统计学差异,表明肠道菌群中大肠杆菌异常可引起siga异常,进而参与imn的发生发展,为imn发病的可能机制之一。3siga与血白蛋白、蛋白尿无相关性,表明前者不能反映imn的临床转归,但siga可能主要参与了imn的发病,可通过探讨前者与肾脏病理学改变如基底膜厚度、免疫复合物沉积程度是否相关进一步研究。
[Abstract]:Objective: membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Its pathological features are the deposition of the immune complex under the epithelia of the glomerular basement membrane and the diffuse thickening of the glomerular basement membrane. The unknown etiology is called idiopathic membranous nephropathy (IMN, IMN). It is reported that the incidence of IMN in our country accounts for 9.54% of all primary glomerular diseases, and the incidence of IMN is increasing year by year. The pathogenesis of MN has not yet been fully elucidated. Therefore, further exploration of the pathogenesis of IMN is of great significance for the diagnosis and guidance of clinical treatment. Intestinal flora, SIgA and intestinal mucosa are of great significance. Permeability, respectively, represents the intestinal mucosal biological barrier, immune barrier and mechanical barrier, and the abnormalities of the intestinal mucosal barrier system may participate in the occurrence and development of autoimmune diseases. Some studies have found that there are cationic bovine serum albumin (BSA) in the MN children, which can be absorbed into the blood through the immature intestinal mucosal barrier in the children. What is the relationship between intestinal mucosal barrier damage and the relationship between intestinal mucosal damage and the incidence of IMN in.IMN patients with MN? This study evaluated the intestinal mucosal biological barrier and immune barrier by detecting the number of intestinal microflora and the level of secretory immunoglobulin A (Secretory immunoglobulin A, SIgA), and discussing the relationship between the intestinal mucosal biological barrier and the immune barrier, in order to be IM. The clinical treatment of N provides scientific guidance and theoretical basis. Methods: 51 cases of IMN were confirmed by biopsy of renal biopsy in the Third Hospital of Hebei Medical University in May 2016, ~2016, and confirmed by immunofluorescence, light microscopy and electron microscopy, as case group (group IMN), 34 men and 17 women, with an average age of 46.57 + 12.88. The average age of BMI was 25.30 + 3.52 kg/m2, and 21 healthy people were selected as the normal control group (healthy control group), including 13 men and 8 women, with an average age of 52.62 + 14.23 years, with an average of BMI 24.65 + 3.01kg/m2. in all IMN patients within 1 months. Before entering the group, the hormone and immunosuppressive agents were not used. The ratio of Bifidobacterium and Escherichia coli (Bifidobacteria/E.coli, B/E) in the faeces was evaluated by the number of Bifidobacteria/E.coli (B/E) in the faeces. Compared with the healthy control group, the decrease of B/E value indicated the application of real-time fluorescent quantitative PCR (real time-PCR, RT-PCR) to detect fecal bifidobacteria and acidophilus milk by the use of real-time quantitative PCR (real time-PCR, RT-PCR). Bacillus, Escherichia coli (escherichiacoli, E.coli) and Enterococcus faecalis, evaluation of intestinal mucosal biological barrier function. Calculation of b/e ratio evaluation of intestinal microecological environment.2 using enzyme linked immunosorbent assay (enzyme-linkedimmunosorbentassay, ELISA) detection of fecal SIgA water level, evaluation of intestinal mucosal immune barrier function.3 to IMN patients early intestine The correlation analysis between the flora, SIgA, b/e values and the blood albumin and urine protein. The correlation analysis between the intestinal flora, the b/e value and the SIgA was carried out. The statistical analysis was carried out by the spss21.0 statistical software. The measurement data of the normal distribution were described with the mean number of standard deviation (x + s), and the median (minimum value maximum) was used for the partial distribution. The measurement data are described; two samples are compared to normal, t test is used when the variance is homogeneous; mann-whitneyu test is used when dissatisfaction is not satisfied; the correlation analysis satisfies the bivariate normal distribution with perason linear correlation analysis, and the difference is statistically significant when the Spearman rank correlation analysis.P0.05 is not satisfied. Results: 1imn group and health Compared with fecal Bifidobacterium, Lactobacillus acidophilus, the number of Enterococcus faecalis and the b/e value, the number of Escherichia coli increased, but the difference was not statistically significant (P0.05) the expression of sIgA in the.2imn group was significantly lower than that in the healthy control group, P0.05, the difference was statistically significant,.3 fecal Bifidobacterium, Lactobacillus acidophilus, E. coli, fecal intestine There was no correlation between b/e value and serum albumin and urine protein (P0.05).Siga and serum albumin, no correlation between urine protein (P0.05). Escherichia coli and SIgA were negatively correlated, r=-0.344, p=0.0130.05; b/e value was positively correlated with SIgA, r=0.382, p=0.0060.05. conclusion: 1 intestinal flora in the early stage of IMN has no abnormal changes, the former is directly related to whether there is The results of further study of.2 showed that Escherichia coli was associated with sIgA in intestinal flora, and the latter was statistically different in IMN, indicating that abnormal Escherichia coli in intestinal flora could cause abnormal SIgA, and then participate in the development of IMN. There was no correlation between.3siga and blood Leucin and proteinuria, which indicated that the former could not reflect I. The clinical outcome of Mn, but SIgA may be mainly involved in the pathogenesis of IMN, can be further studied by discussing whether the former is related to the pathological changes of the kidney, such as the thickness of the basement membrane and the degree of immune complex deposition.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692

【参考文献】