本文選題：膜性腎病 + 特發(fā)性�。� 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:膜性腎病(membranous nephropathy,MN)是引起成人腎病綜合征最常見的病因,其病理學(xué)特征為腎小球基底膜外臟層上皮細(xì)胞下免疫復(fù)合物的沉積伴腎小球基底膜彌漫性增厚,病因不明者稱為特發(fā)性膜性腎病(idiopathic membranous nephropathy,IMN)。有研究報(bào)道,我國(guó)IMN發(fā)病率占全部原發(fā)性腎小球疾病的9.54%,而且IMN的發(fā)生率呈逐年升高的趨勢(shì)。目前MN的發(fā)病機(jī)制尚未完全闡明,因此進(jìn)一步探究IMN的發(fā)病機(jī)制對(duì)于明確疾病診斷和指導(dǎo)臨床治療有著重要意義。腸道菌群、SIgA和腸粘膜通透性分別代表腸粘膜生物屏障、免疫屏障和機(jī)械屏障,腸粘膜屏障系統(tǒng)的異常可能參與了自身免疫性疾病的發(fā)生和發(fā)展。有研究發(fā)現(xiàn)MN患兒體內(nèi)存在陽(yáng)離子牛血清白蛋白(BSA),其在未分解時(shí)可能透過患兒未成熟的腸粘膜屏障吸收入血,導(dǎo)致MN的發(fā)生。IMN患者是否存在腸粘膜屏障損傷?腸粘膜損傷與IMN的發(fā)病關(guān)系如何?本研究通過檢測(cè)腸道菌群數(shù)量和分泌型免疫球蛋白A(Secretory immunoglobulin A,SIgA)水平來評(píng)價(jià)腸粘膜生物屏障和免疫屏障,探討其與IMN發(fā)病的關(guān)系,以期為IMN的臨床治療提供科學(xué)指導(dǎo)和理論依據(jù)。方法:選取2016年5月~2016年12月在河北醫(yī)科大學(xué)第三醫(yī)院腎內(nèi)科住院,腎穿刺病理活檢,并經(jīng)免疫熒光、光鏡和電鏡證實(shí)為IMN的患者51例,作為病例組(IMN組),其中男性34人,女性17人,平均年齡46.57±12.88歲,平均BMI 25.30±3.52 kg/m2;選取同期來我院體檢的健康人21例,作為正常對(duì)照組(健康對(duì)照組),其中男性13人,女性8人,平均年齡52.62±14.23歲,平均BMI 24.65±3.01kg/m2。所有IMN患者發(fā)病時(shí)間均在1個(gè)月內(nèi),入組前未應(yīng)用激素及免疫抑制劑治療。收集入組者清晨空腹第一次糞便標(biāo)本。糞便中雙歧桿菌與大腸桿菌數(shù)量之比(Bifidobacteria/E.coli,B/E)評(píng)價(jià)腸道微生態(tài)環(huán)境。和健康對(duì)照組相比,B/E值降低說明腸道菌群失調(diào)。1應(yīng)用實(shí)時(shí)熒光定量PCR(real time-PCR,RT-PCR)技術(shù)檢測(cè)糞便雙歧桿菌、嗜酸乳桿菌、大腸桿菌(escherichiacoli,e.coli)和糞腸球菌的含量,評(píng)價(jià)腸粘膜生物屏障功能。計(jì)算b/e比值評(píng)價(jià)腸道微生態(tài)環(huán)境。2采用酶聯(lián)免疫吸附測(cè)定法(enzyme-linkedimmunosorbentassay,elisa)檢測(cè)糞便siga水平,評(píng)價(jià)腸粘膜免疫屏障功能。3對(duì)imn患者早期腸道菌群、siga、b/e值與血白蛋白、尿蛋白分別進(jìn)行相關(guān)分析。對(duì)腸道菌群、b/e值與siga之間互相進(jìn)行相關(guān)分析。采用spss21.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)分析。采用均數(shù)±標(biāo)準(zhǔn)差(x±s)對(duì)正態(tài)分布的計(jì)量資料進(jìn)行描述;采用中位數(shù)(最小值-最大值)對(duì)偏態(tài)分布的計(jì)量資料進(jìn)行描述;兩樣本均數(shù)比較滿足正態(tài)、方差齊時(shí)采用t檢驗(yàn);不滿足時(shí)采用mann-whitneyu檢驗(yàn);相關(guān)分析滿足雙變量正態(tài)分布時(shí)采用perason直線相關(guān)分析,不滿足時(shí)采用spearman秩相關(guān)分析。p0.05時(shí)差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1imn組與健康對(duì)照組相比糞便雙歧桿菌、嗜酸乳桿菌、糞腸球菌數(shù)量和b/e值均下降,大腸桿菌數(shù)量增加,但差異均無統(tǒng)計(jì)學(xué)意義(p0.05)。2imn組與健康對(duì)照組相比糞便siga表達(dá)量明顯下降,p0.05,差異有統(tǒng)計(jì)學(xué)意義。3糞便雙歧桿菌、嗜酸乳桿菌、大腸桿菌、糞腸球菌及b/e值與血白蛋白、尿蛋白均無相關(guān)性(p0.05)。siga與血白蛋白、尿蛋白均無相關(guān)性(p0.05)。大腸桿菌與siga呈負(fù)相關(guān),r=-0.344,p=0.0130.05;b/e值與siga呈正相關(guān),r=0.382,p=0.0060.05。結(jié)論:1腸道菌群在imn早期沒有異常變化,前者與imn是否直接相關(guān)有待進(jìn)一步研究。2結(jié)果顯示腸道菌群中大腸桿菌與siga相關(guān),后者在imn中有統(tǒng)計(jì)學(xué)差異,表明腸道菌群中大腸桿菌異�？梢餾iga異常,進(jìn)而參與imn的發(fā)生發(fā)展,為imn發(fā)病的可能機(jī)制之一。3siga與血白蛋白、蛋白尿無相關(guān)性,表明前者不能反映imn的臨床轉(zhuǎn)歸,但siga可能主要參與了imn的發(fā)病,可通過探討前者與腎臟病理學(xué)改變?nèi)缁啄ず穸�、免疫�?fù)合物沉積程度是否相關(guān)進(jìn)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.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R692

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