本文選題：VEGF　切入點：VEGFR-1　出處：《山東大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景：IgA腎病是原發(fā)性腎小球腎炎的常見的病理類型之一,發(fā)病率較高,已經(jīng)成為終末期腎病常見的原發(fā)病,因此識別IgA腎病的危險因素,并早期給予干預(yù)具有重要的臨床意義。目前國內(nèi)國外已有大量研究顯示血管內(nèi)皮生長因子(VEGF)及其受體(VEGFR-1和VEGFR-2)在多種腎小球疾病如：腎小球輕微病變性腎病,膜性腎病,狼瘡性腎炎,糖尿病腎病等疾病中的表達(dá)與正常人腎組織中的表達(dá)有差別,其表達(dá)的異常與疾病預(yù)后密切相關(guān)。 目的：研究VEGF及其受體VEGFR-1、VEGFR-2在IgA腎病病人腎臟局部組織的表達(dá)情況,及其與IgA腎病病人蛋白尿轉(zhuǎn)歸的相關(guān)性。 方法：選取2005-2008年在山東省立醫(yī)院行腎穿刺活檢,病理確診為工gA腎病的病人49例,追蹤記錄患者年齡,性別,體重,血壓,24小時尿蛋白定量,血白蛋白,血脂,血肌酐,血中IgA、C3、尿酸水平等臨床資料,規(guī)律隨訪1年以上。通過免疫組織化學(xué)方法檢測病人腎穿刺活檢組織中小球、小管以及間質(zhì)中VEGF、VEGFR-1、VEGFR-2的表達(dá)水平,并請專業(yè)病理醫(yī)師對其表達(dá)水平進行評分。根據(jù)病人腎穿刺活檢前24小時尿蛋白定量及腎臟病理病變程度分別分組,探究VEGF、VEGFR-1. VEGFR-2在各組中分別在小球、小管、間質(zhì)中的表達(dá)情況,并應(yīng)用T檢驗檢測各組之間差異性。以病人1年后蛋白尿轉(zhuǎn)歸情況為觀測指標(biāo),應(yīng)用Logistic回歸分析分析相關(guān)因素(如：年齡,性別,基線蛋白尿,血白蛋白,血肌酐,血中IgA、C3、尿酸水平,病理分級,腎小球濾過率,治療方案等)對病人蛋白尿轉(zhuǎn)歸的影響。探究VEGF、VEGFR-1、VEGFR-2的表達(dá)與IgA腎病病人預(yù)后的相關(guān)性。 結(jié)果：1.根據(jù)患者腎穿刺活檢時24小時尿蛋白定量分組,將24小時尿蛋白定量小于等于1.0g者定義為A組,24小時尿蛋白定量介于1.0g-3.5g者定義為B組,24小時尿蛋白定量大于等于3.5g者定義為C組；VEGFR-2在C組中表達(dá)高于B組(8.37±5.36VS4.78±4.27),P=0.035,有統(tǒng)計學(xué)意義；在其它兩組中表達(dá)無明顯差別；VEGF及VEGFR-1在三組中表達(dá)均未見明顯差別(P0.05)。VEGF,VEGFR-1及VEGFR-2在小球中的表達(dá)三組未見明顯差別(P0.05),但VEGFR-2在小管間質(zhì)中的表達(dá)C組中高于B組(4.12±3.05VS2.36±2.03,P=0.012),有統(tǒng)計學(xué)差別。 2.根據(jù)牛津分型腎小管萎縮及間質(zhì)纖維化程度(T)分組,T大于等于1分的定義為T1組,T等于0分的定義為T0組,VEGF表達(dá)在兩組中有明顯差異(8.43±4.72VS4.98±4.12,P=0.040)；VEGFR-1、VEGFR-2在T0組及T1組表達(dá)無明顯差異。 3.根據(jù)腎臟組織中新月體數(shù)目多少分組,分為有新月體形成組及無新月體形成組,兩組中有新月體形成組VEGF表達(dá)減低,有統(tǒng)計學(xué)差異(3.00±2.68VS5.81±4.41,P0.05)；新月體形成組VEGFR-2表達(dá)減低,有統(tǒng)計學(xué)差異(1.80±1.30VS6.59±5.23,P0.05)；VEGFR-1表達(dá)在有新月體形成組及無新月體形成組未見統(tǒng)計學(xué)差異。 4.以病人1年后蛋白尿轉(zhuǎn)歸情況為觀測指標(biāo),Logistic回歸分析顯示VEGF表達(dá)水平是蛋白尿轉(zhuǎn)歸的危險因素。此外年齡、舒張壓、膽固醇水平是蛋白尿轉(zhuǎn)歸的危險因素。 結(jié)論：IgA腎病中VEGF及VEGFR-2主要在腎小管間質(zhì)中高表達(dá),并且與蛋白尿轉(zhuǎn)歸密切相關(guān),提示VEGF/VEGFR-2為影響IgA腎病預(yù)后的重要因子。
[Abstract]:Background: IgA nephropathy is one of the most common pathological type of primary glomerulonephritis, high incidence, incidence of end-stage renal disease has become the common risk factors, therefore the recognition of IgA nephropathy, and early intervention has important clinical significance. At present, the domestic foreign research shows that vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) in various glomerular diseases such as: minor glomerular lesions nephropathy, membranous nephropathy, lupus nephritis, renal tissue expression in diabetic nephropathy and normal people in different anomalies and its expression is closely related to the prognosis of the disease.
Objective: To investigate the expression of VEGF and its receptor VEGFR-1 and VEGFR-2 in renal tissue of patients with IgA nephropathy and its correlation with proteinuria in patients with IgA nephropathy.
Methods: a total of 2005-2008 years in Shangdong Province-owned Hospital underwent renal biopsy, pathological diagnosis of 49 cases of gA nephropathy patients, track of patient age, gender, body weight, blood pressure, 24 hour urinary protein, serum albumin, blood lipid, serum creatinine, blood IgA, C3, clinical data of uric acid water equality, rule of 1 years of follow-up the ball above. Through the detection of patients renal biopsy and immunohistochemical method, tubular and interstitial in VEGF, VEGFR-1, VEGFR-2 expression, and the expression level of professional pathologists please wasassessed. According to the patients with renal biopsy before 24 hours urine protein and renal pathological lesions were grouped on VEGF VEGFR-1., VEGFR-2 respectively in the tubular ball, in each group, the expression in the stroma, and the application of T test between groups. The differences in patient outcomes after 1 years of proteinuria were observed by Logistic Regression analysis of related factors (such as age, gender, baseline proteinuria, serum albumin, serum creatinine, blood uric acid, IgA, C3, pathological grading, glomerular filtration rate, treatment effect on the outcome of patients with proteinuria). On VEGF, VEGFR-1, correlation between VEGFR-2 expression and prognosis of IgA nephropathy patients.
Results: 1. patients with renal biopsy under 24 hour urinary protein quantitative group, 24 hour urinary protein quantity is less than or equal to 1.0g were defined as A group, 24 hour urinary protein between 1.0g-3.5g were defined as B group, 24 hour urinary protein quantity is greater than or equal to 3.5G were defined as C group; the expression of VEGFR-2 in the C group higher than that of group B (8.37 + 5.36VS4.78 + 4.27, P=0.035), there was statistical significance; expression had no significant difference in the other two groups had no significant difference; the expression of VEGF and VEGFR-1 in the three groups (.VEGF, P0.05) expression of the three groups was no obvious difference between VEGFR-1 and VEGFR-2 in the ball in (P0.05), but in VEGFR-2 tubulointerstitial expression in C group was higher than that of group B (4.12 + 3.05VS2.36 + 2.03, P=0.012), the difference was statistically significant.
2. according to the Oxford classification of renal tubular atrophy and interstitial fibrosis (T) group, T is greater than or equal to 1 points defined as group T1, T is equal to 0 points defined as group T0, VEGF expression was significantly different in the two groups (8.43 + 4.72VS4.98 + 4.12, P=0.040); VEGFR-1, VEGFR-2 in T0 group and T1 group showed no significant difference.
3. according to the crescent kidney body number grouping, divided into the formation of Crescent Group and no crescent formation group, two groups in the formation of Crescent Group reduce the expression of VEGF, there were significant differences (3 + 2.68VS5.81 + 4.41, P0.05); crescent formation reduced group VEGFR-2 expression, there were significant differences (1.80. 1.30VS6.59 + 5.23, P0.05); the expression of VEGFR-1 in the formation of crescent and the crescent formation group had no significant difference.
4., after 1 years' prognosis of proteinuria as observation index, Logistic regression analysis showed that VEGF expression is a risk factor of proteinuria prognosis. Besides, age, diastolic blood pressure and cholesterol level are risk factors of proteinuria prognosis.
Conclusion: VEGF and VEGFR-2 in IgA nephropathy are highly expressed in tubulointerstitium, and are closely related to the prognosis of proteinuria, suggesting that VEGF/VEGFR-2 is an important factor affecting the prognosis of IgA nephropathy.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R692.31

【共引文獻(xiàn)】

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1 向少偉;黃國東;黃仁發(fā);賀西南;賴申昌;許健;;復(fù)方仙草顆粒對IgA腎病大鼠轉(zhuǎn)化生長因子β_1及其Ⅱ型受體表達(dá)的影響[J];安徽中醫(yī)學(xué)院學(xué)報;2013年04期

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