【作者】 唐雪梅；

【导师】 李秋；

【作者基本信息】 重庆医科大学 ， 儿科学， 2004， 硕士

【摘要】 目的： 研究转化生长因子β1（TGF－β1）和血管内皮生长因子（VEGF）与儿童原发性肾病综合征（PNS）蛋白尿的关系及其在不同病理类型肾组织中的表达差异，探讨PNS蛋白尿的发生机理及肾小球疾病肾组织纤维化的影响因素，指导治疗，判断预后。方法： 应用酶联免疫吸附双抗体夹心法（ELISA）测定正常对照组10例、NS组患儿28例的血清TGF－β1、VEGF水平，比较两指标血清水平变化与蛋白尿之间、与肾病不同病理类型之间的关系及两者的相关性；应用免疫组织化学S-P二步法检测12例不同病理类型NS肾组织及3例正常肾组织中TGF－β1、VEGF的蛋白表达情况，并比较其差异。结果： 1.蛋白尿阳性NS组，其血清TGF－β1、VEGF水平均分别较正常组和蛋白尿阴性NS组显著增高（P<0.05），且两指标之间呈正相关（r =0.4305）。 2. 在NS不同病理类型中，FSGS组血清TGF－β1水平较MCNS、MSPGN组及对照组显著升高(P<0.01)。 3. FSGS及MSPGN组血清VEGF水平较MCNS及对照组显著增高(P<0.01)。 4. TGF－β1、VEGF在NS组病变肾组织中阳性表达面积均显著高于对照组(P<0.01)。 5. TGF－β1的蛋白表达强度在MCNS、MSPGN、MN、 FSGS四组中呈逐渐增强趋势，尤其在伴间质纤维化组，TGF－β1表达较无纤维化组明显增强，其差异具有显著性（P<0.05）；而VEGF蛋白表达强度在NS不同病理类型之间以及有无间质纤维化之间差异无显著性(P>0.05)。 结论： 1. 血清TGF－β1、VEGF水平与NS蛋白<WP=6>尿的产生有关，且与肾脏病理损害类型有关。 2. NS病人肾组织均存在TGF－β1、VEGF蛋白表达增强,尤以TGF－β1表达增强为著,且其表达强度与肾小管间质纤维化程度有关。3.抗VEGF和 TGF－β1的研究和应用可能是治疗NS蛋白尿及改善本病预后，防止肾纤维化的重要手段。更多还原

【Abstract】 Objective To study the relationship of transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF) with proteinuria in children with primary nephrotic syndrome(PNS) and the expression discrepancy in varied pathology type by renal biopsy and to explore mechanism of the proteinuria and influence factors of fibrosis in PNS in order to guide the treatment and to judge the prognosis. Methods Twenty-eight patients were as test group, and ten healthy children were as control group. In test group 7 cases were in remission and others were divided into three groups which were confirmed by renal biopsy: minimal change nephrotic syndrome (MCNS) in 5 patients, mesangial proliferative glomerulonephritis (MSPGN) in 12 and focal segmental glomerulo- sclerosis (FSGS) in 4. The peripheral blood serum levels for the protein of TGF-β1 and VEGF were measured by enzyme-linked immunosorbent assay (ELISA), comparing the associated for their serum levels of protein with proteinuria and pathologic types. The protein expression of TGF-β1 and VEGF were analysed by immunohistochemistry staining with streptavidin-peroxidase in nephritic tissues of different pathologic types in twelve cases and control group in three . Results 1.The protein levels of TGF-β1, VEGF in blood serum were higher in the test group with proteinuria than remission (P<0.05), and there was positive relation between the two index（r =0.4305）.2. The protein levels of TGF-β1 in blood serum was much higher in FSGS than MCNS, MSPGN and control (P<0.01). 3. The protein levels of VEGF in blood serum was much higher in FSGS and MSPGN than MCNS and control group (P<0.01). 4. The expression for positive area of TGF-β1 and VEGF were much higher in nephritic tissues with NS than that with <WP=8>control group(P<0.01). 5. The expression for positive intensity of TGF-β1 protein was higher and higher in different nephritic tissues from MCNS, MSPGN, MN to FSGS, especially the increasing expression of TGF-β1 which was associated with fibrosis degree of tubule and interstitial, and there were statistical significance (P<0.01). But the expression for positive intensity of VEGF protein was no statistical significance in all test groups include interstitial fibrosis (P>0.05). Conclusions 1. Serum levels of TGF-β1 and VEGF were associated with proteinuria and different types of pathology in children with primary nephrotic syndrome. 2. Positive expression intensity of TGF-β1 and VEGF in nephritic tissues was higher in PNS than in control group, especially the increasing expression of TGF-β1 which was associated with fibrosis degree of tubule and interstitial in PNS. 3. Anti-VEGF and Anti- TGF-β1 may be a important means in treating proteinuria, improving the prognosis and preventing the fibrosis in PNS.更多还原