Ⅱ型糖尿病患者血清和肾组织糖基化终末期产物的检测及意义

IMMUNOCHEMICAL DETECTION OF AGES IN NON INSULIN DEPENDENT DIABETES MELLITUS PATIENTS

目的：进一步阐明血清和肾组织糖基化终末期产物（ＡＧＥｓ）在非胰岛素依赖型糖尿病（ＮＩＤＤＭ）发病机理中的意义。方法：首次在国内应用竞争性ＥＬＩＳＡ对２６例ＮＩＤＤＭ患者血清ＡＧＥｓ和ＰＡＰ三层法对其中１７例伴糖尿病肾病（ＤＮ）的ＮＩＤＤＭ患者肾组织中ＡＧＥｓ进行了检测，并结合临床表现和病理改变加以分析。结果：２６例ＮＩＤＤＭ患者血清ＡＧＥｓ为３４．２６±１４．５３ｍｇ／Ｌ，较同年龄正常对照组显著升高（Ｐ＜０．０１），合并眼底改变者较无眼底改变者血清ＡＧＥｓ明显增加（Ｐ＜０．０５），肾功能损害者（Ｓｃｒ＞１３４μｍｏｌ／Ｌ）较肾功能正常者血清ＡＧＥｓ上升幅度更为明显（Ｐ＞０．０５）。血清ＡＧＥｓ水平与血清糖化血红蛋白（ＨｂＡｌｃ）呈正相关（ｒ＝０．６１０４，Ｐ＜０．０１）。ＡＧＥｓ弥漫分布于肾组织，与文献报告系膜区ＡＧＥｓ广泛沉积不同的是本组患者仅１例系膜区ＡＧＥｓ阳性。不同部位肾组织ＡＧＥｓ阳性者均较ＡＧＥｓ阴性者临床表现和（或）病理改变明显加重或出现加量趋势。结论：血清ＡＧＥｓ在ＮＩＤＤＭ患者明显升高，与血清ＨｂＡｌｃ呈正相关，并与ＮＩＤＤＭ患者眼底病变有一定的关联，糖尿病伴肾脏损害是血清ＡＧＥｓ水平升高?

OBJECTIVE To elucidate the role of advanced glycation end products(AGEs) in the pathogenesis of non insulin dependent diabetes mellitus(NIDDM). METHODOLOGY Serum AGEs in 26 NIDDM patients and 26 age matched normal controls were determined by competitive ELISA. AGEs in renal biopsy tissue from 17 NIDDM patients with diabetic nephropathy were detected by 3 layer PAP assay. Clinical and renal pathological data were analyzed. RESULTS Serum AGEs in NIDDM patients were significantly higher than that of normal controls (36 26±14 53 vs 20 34±6 17 U/ml, P <0 01); Patients with diabetic retinopathy( n =12) showed a higher level of serum AGEs than those without diabetic retinopathy ( n =14) (41 35±13 69 vs 28 20±12 72, P <0 05). There was an increasing trend of serum AGEs level in patients with renal failure (serum creatinine>132 6 μmol/L, n =8) than in patients without renal failure ( n =18)(39 20±16 33 vs 32 04±13 59, P >0 05). A positive correlated of serum AGEs with hemoglobin A1c level ( r =0 61038, P <0 01) was found. AGEs deposited extensively in renal tissue,but rarely in the mesangium. Patients with glomerular AGEs deposition tended to have severe tubulointerstitial and glomerular sclerosis. CONCLUSION Serum AGEs elevated significantly in NIDDM patients, and was positively correlated with serum hemoglobin A1c. High level of serum AGEs are associated with the development of diabetic rentinopathy. Diabetic nephropathy is one of the factors contributing to elevated serum AGEs. Extensive deposition of AGEs was found in renal tissue of patients with diabetic nephropathy. AGEs deposition in different part of renal tissue related with clinical manifestation and renal histopathological changes.