VEGF及其受体在IgA肾病中的表达

发布时间：2018-03-22 02:18

本文选题：VEGF　切入点：VEGFR-1　出处：《山东大学》2014年硕士论文　论文类型：学位论文

【摘要】：研究背景：IgA肾病是原发性肾小球肾炎的常见的病理类型之一,发病率较高,已经成为终末期肾病常见的原发病,因此识别IgA肾病的危险因素,并早期给予干预具有重要的临床意义。目前国内国外已有大量研究显示血管内皮生长因子(VEGF)及其受体(VEGFR-1和VEGFR-2)在多种肾小球疾病如：肾小球轻微病变性肾病,膜性肾病,狼疮性肾炎,糖尿病肾病等疾病中的表达与正常人肾组织中的表达有差别,其表达的异常与疾病预后密切相关。目的：研究VEGF及其受体VEGFR-1、VEGFR-2在IgA肾病病人肾脏局部组织的表达情况,及其与IgA肾病病人蛋白尿转归的相关性。方法：选取2005-2008年在山东省立医院行肾穿刺活检,病理确诊为工gA肾病的病人49例,追踪记录患者年龄,性别,体重,血压,24小时尿蛋白定量,血白蛋白,血脂,血肌酐,血中IgA、C3、尿酸水平等临床资料,规律随访1年以上。通过免疫组织化学方法检测病人肾穿刺活检组织中小球、小管以及间质中VEGF、VEGFR-1、VEGFR-2的表达水平,并请专业病理医师对其表达水平进行评分。根据病人肾穿刺活检前24小时尿蛋白定量及肾脏病理病变程度分别分组,探究VEGF、VEGFR-1. VEGFR-2在各组中分别在小球、小管、间质中的表达情况,并应用T检验检测各组之间差异性。以病人1年后蛋白尿转归情况为观测指标,应用Logistic回归分析分析相关因素(如：年龄,性别,基线蛋白尿,血白蛋白,血肌酐,血中IgA、C3、尿酸水平,病理分级,肾小球滤过率,治疗方案等)对病人蛋白尿转归的影响。探究VEGF、VEGFR-1、VEGFR-2的表达与IgA肾病病人预后的相关性。结果：1.根据患者肾穿刺活检时24小时尿蛋白定量分组,将24小时尿蛋白定量小于等于1.0g者定义为A组,24小时尿蛋白定量介于1.0g-3.5g者定义为B组,24小时尿蛋白定量大于等于3.5g者定义为C组；VEGFR-2在C组中表达高于B组(8.37±5.36VS4.78±4.27),P=0.035,有统计学意义；在其它两组中表达无明显差别；VEGF及VEGFR-1在三组中表达均未见明显差别(P0.05)。VEGF,VEGFR-1及VEGFR-2在小球中的表达三组未见明显差别(P0.05),但VEGFR-2在小管间质中的表达C组中高于B组(4.12±3.05VS2.36±2.03,P=0.012),有统计学差别。 2.根据牛津分型肾小管萎缩及间质纤维化程度(T)分组,T大于等于1分的定义为T1组,T等于0分的定义为T0组,VEGF表达在两组中有明显差异(8.43±4.72VS4.98±4.12,P=0.040)；VEGFR-1、VEGFR-2在T0组及T1组表达无明显差异。 3.根据肾脏组织中新月体数目多少分组,分为有新月体形成组及无新月体形成组,两组中有新月体形成组VEGF表达减低,有统计学差异(3.00±2.68VS5.81±4.41,P0.05)；新月体形成组VEGFR-2表达减低,有统计学差异(1.80±1.30VS6.59±5.23,P0.05)；VEGFR-1表达在有新月体形成组及无新月体形成组未见统计学差异。 4.以病人1年后蛋白尿转归情况为观测指标,Logistic回归分析显示VEGF表达水平是蛋白尿转归的危险因素。此外年龄、舒张压、胆固醇水平是蛋白尿转归的危险因素。结论：IgA肾病中VEGF及VEGFR-2主要在肾小管间质中高表达,并且与蛋白尿转归密切相关,提示VEGF/VEGFR-2为影响IgA肾病预后的重要因子。
[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.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692.31

【共引文献】