摘要
目的:观察一种新发现的血管生成相关生长因子血管生成素样蛋白2(ANGPTL2)在糖尿病肾病(diabeticnephropathy,DN)肾小球中的表达特征,并对其在DN发生发展过程中可能的作用机制进行初步探讨。方法:采用肾活检组织肾小球微分离技术结合半定量RTPCR方法,观察24例2型DN患者肾小球中ANGPTL2mRNA表达情况,以8例移植供肾活检组织作正常对照。并将其表达水平与DN患者临床病理指标进行相关分析。结果:DN患者肾小球ANGPTL2表达阳性率显著高于对照组(95%vs38%,χ2=15.9,P<0.01)。在表达明显上调(>2倍)的患者中,肾小球微血管瘤、内皮细胞炎性浸润与泡沫化变性的发生率明显少于其他患者(22%vs66%;11%vs73%;11%vs53%;P<0.05)。结论:ANGPTL2是一种血管生成相关的内皮细胞生长调节因子,参与DN微血管病变的发生机制。该因子在糖尿病肾小球中表达的上调可能是内皮损伤与血管重构过程中的一种应激性反应,具有维持内皮细胞功能与毛细血管正常结构的保护性作用。
Objective:Microvascular angiogenesis plays an important role in the development of diabetic nephropathy ( DN ). We identified in our previous gene chip screening study that angiopoietin-like protein 2 ( ANGPTL 2 ), as a novel DN associated growth factor, was implicated in the diabetic microvascular lesion. In this study, we investigated the characteristics of ANGPTL 2 expression at both mRNA level and protein level in the microvascular lesion of DN. nethodology:Glomeruli were microdissected from renal biopsy specimen of 24 DN patients, and the expression of ANGPTL 2 gene was evaluated by semi-quantitative RT-PCR. The correlations between ANGPTL 2 expression and patients' phenotypic characteristics were explored. Results:In consistent with the results obtained from gene chip, a significant upregulation of ANGPTL 2 expression was found in glomeruli from DN patients, as compared with the normal controls (95% vs 38%, χ^2 = 15.9, P 〈 0.01 ). The pronounced upregnlation of ANGPTL 2 expression was found in DN patients with less microaneurysm formation ( 22% vs 66% , P 〈 0.05 ) , fewer infiltrating leukocytes ( 11% vs 73 % , P 〈 0. 05 ) and fewer endothelial foam cell( 11% vs 53% , P 〈 0. 05 ) in the glomeruli. Conclusion : Enhanced glomerular expression of ANGPTL 2 is reversely correlated with glomerular endothelialium abnormalities in DN patients. This upregnlated expression may be a protective response in maintaining the normal capillary arrangement as well as endothelial function in glomeruli in diabetic patients.
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
2005年第6期531-535,共5页
Chinese Journal of Nephrology,Dialysis & Transplantation
基金
国家自然科学基金(NO:30470801)
江苏省自然基金项目(BK2005086)