尿Ⅳ型胶原: 一种早期糖尿病肾病的预测指标
Urinary type Ⅳ collagen: a specific indicator of incipient diabetic nephropathy
摘要目的 研究尿Ⅳ型胶原(IVC)对糖尿病肾病(DN)的特异性诊断价值.方法 应用我们建立的一种新的ABC-ELISA直接检测尿IVC,选取120例2型糖尿病病人(DM) 及多组对照作为研究对象,复管测定24小时尿IVC排泄率(UCER);同时应用RIA方法复管测定24小时尿白蛋白排泄率(UAER).为了明确DN的病变程度,有13例伴微量白蛋白尿的DM病人行肾穿刺活检术,并且应用ABC法研究肾脏IVC、TGF-β 1的免疫沉积.结果 DM病人的UCER较各对照组均明显升高,尤其在UAER 201-300?mg/24 h亚组升高得更加显著(P<0.01);而在蛋白尿阴性的DM病人,UCER则与正常对照组、原发性肾小球肾炎组(IgA肾炎、膜性肾病、微小病变型肾炎)、原发性高血压组和冠心病组无显著性差别.在DM病人中,尿IVC与Ccr呈显著负相关(r=-0.41, P<0.001).在尿IVC升高的DM病人,其肾脏呈显著的DN病变特征,如细胞外基质的扩张,基底膜的增厚,伴肾小球、Bowman氏囊及间质的IVC、TGF-β 1的大量沉积.结论 尿IVC,可能为其合成增加和/或降解减少的反映,有可能成为预测早期DN的有价值的临床指标.
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abstractsObjective To determine whether urinary type Ⅳ collagen can serve as an indicator specific for diabetic nephropathy. Methods Using a novel sandwich ABC-ELISA to measure type Ⅳ collagen directly, the 24-hour urinary type Ⅳ collagen excretion rate was determined in 120 diabetic patients and some groups of controls. Urinary albumin determinations were made with a RIA kit at the same time. A total of 13 diabetic patients with microalbuminuria underwent percutaneous renal biopsy for definitive diagnosis of diabetic nephropathy. Type Ⅳ collagen and TGF-beta 1 immunoreactivities were detected with ABC methods in renal biopsies. Results Urinary type Ⅳ collagen excretion was significantly increased in diabetic patients with microalbuminuria, especially those with albumin excretion above 200?mg/24?h. By comparison, collagen excretion was equivalent to that in healthy controls when measured in diabetics with normalbuminuria and in patients with primary glomerular disease, primary hypertension, or coronary heart disease. Urinary type Ⅳ collagen excretion in diabetics was negatively correlated with creatinine clearance. In renal biopsies from subjects with elevated collagen excretion, the glomeruli showed pathological changes typical of diabetic nephropathy. Also, excessive type Ⅳ collagen and TGF-beta 1 immunoreactivity were detected in the glomeruli, Bowman's capsule and interstitium. Conclusions Excretion of type Ⅳ collagen, possibly reflecting increased production or decreased degradation of this protein, may be a clinically useful indicator of incipient diabetic nephropathy. z
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