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糖尿病肾病大鼠肾小管与肾小球病变的顺序及其意义 被引量:32

Research on the subsequence of pathological changes of glomerulus and renal tubules in rats with diabetic nephropathy and its significance
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摘要 目的 通过IV型胶原 (CⅣ)的测定 ,探讨糖尿病肾病 (DN)大鼠肾小管与肾小球病变的先后顺序及其意义。 方法 尾静脉注射链脲佐菌素 (STZ)建立糖尿病 (DM )大鼠模型。应用放射免疫、免疫组化、电镜、图像自动分析仪对影像数字化处理方法 ,检测DM大鼠不同阶段尿中CⅣ 和白蛋白 (UAlb)含量、肾小球与肾小管内CⅣ 含量、肾小球平均体积 (VG)、PAS阳性物质含量、肾小球基底膜 (GBM )与肾小管基底膜 (TBM )厚度。 结果  ( 1)DM大鼠的尿CⅣ 、UAlb、肌酐清除率 (Ccr)、VG均显著高于对照组 (NC)。 ( 2 )第 2周 ,DM大鼠尿CⅣ 增高 97 1% ,UAlb仅增高 2 3 7% ,此时 ,肾小管内CⅣ 含量增高 ,电镜下TBM出现局限性增厚 ;第 3周 ,肾小管内CⅣ 含量进一步增加 ,TBM出现显著的弥漫性增厚。在此阶段 ,肾小球内CⅣ 含量及GBM厚度均无明显变化 ,直至第 6周 ,肾小球内CⅣ含量才显著增高 ,GBM也出现显著的增厚 ,但其增厚幅度比TBM增厚幅度小。 ( 3)UAlb正常的DM大鼠 ,有 71 4 %尿CⅣ 增高 ,但其肾小球内CⅣ 含量无变化 ,肾小管内却显著增多。 ( 4 )尿CⅣ 与血肌酐 (Cr)、UAlb呈正相关 (r分别为 0 6 3,0 88,P均 <0 0 0 1) ,与PAS灰度、Ccr呈负相关 (r分别为 -0 71,- 0 4 5 ,P均 <0 0 0 1)。 结论  ( 1)DN早期 ,尿C? Objective To probe the subsequence of pathological changes of glomerulus and renal tubules in rats with diabetic nephropathy and its significance by observing the change of type Ⅳ collagen Methods The diabetic rats were made by intravenous injection of streptozotocin Type Ⅳ collagen in urine and kidney were measured by radioimmunoassay and immunohistochemistry respectively Meanwhile computer was used to quantitate the levels of Type Ⅳ collagen in glomerulus and renal tubules, glomerular volume, the content of PAS postitve material and basement membranes thickness Results (1) The levels of urine albumin and urine type Ⅳ collagen, volumes of glomerulus and creatinine clearance were significantly higher in diabetic rats compared with those in control animals (2) At 2 weeks, urine albumin increased only by 23 7%, while urine type Ⅳ collagen increased by 97 1% Type Ⅳ collagen level in renal tubules increased significantly, meanwhile, the tubular basement membrane became locally thick under electron microscope At 3 weeks, the level of type Ⅳ collagen in tubules increased much more and the thickness of tubular basement membrane became obviously diffusely thick Whereas, the level of type Ⅳ collagen in glomerulus and the thickness of glomerular basement membrane did not change during the same period of time compared with those of control animals At 6 weeks, the glomerulus type Ⅳ collagen level raised significantly and the glomerular basement membrane also became thick obviously But scope of increasing was much lower than that of tubules (3) The level of type Ⅳ collagen in tubules, not in glomerulus, increased significantly in 71 4% rats whose urine albumin excretion was normal but urine type Ⅳ collagen excretion was high (4) The level of urine type Ⅳ collagen was positively correlated with urinal albumin ( r=0 88, P < 0 001) and blood creatinine (0 63, P <0 001) and negatively correlated with creatinine clearance ( r=-0 71, P <0 001) and the content of PAS positive material ( r=-0 45, P <0 001) Conclusions (1)Urine type IV collagen increases prior to urinal albumin in the early stage of diabetic nephropathy The increased urine type IV collagen mainly comes from renal tubules, so the pathological changes of tubules was earlier than that of glomerulus in diabetic nephropathy (2) Urine type Ⅳ collagen is more sensitive than urinal albumin in the early diagnosis of DN, and may become a useful marker to monitor the development of DN
出处 《中国糖尿病杂志》 CAS CSCD 2004年第3期219-224,共6页 Chinese Journal of Diabetes
关键词 糖尿病肾病 大鼠 肾小管 肾小球 DN Ⅳ型胶原 Diabetic nephropathy Type Ⅳ collagen Glomerulus Renal tubules
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参考文献5

  • 1Kotajima N,Kimura T,Kanda T,et al. Type Ⅳ collagen as an early marker for diabetic nephropathy in non-insulin-dependent diabetes mellitus: J Diabetes Complications, 2000, 14:13-17.
  • 2Ryuichi K, Masaki T, Motohide I, et al. Mechanism of the progression of diabetic nephropathy to renal failure. Kidney Int,1997,52 (supp62) s39-s40.
  • 3Iijima T, Suzu-ki S, Sekizuka K, et al. Follow-up study on urinary Ⅳ collagen in patients with early stage diabetic nephropathy. J Clin Lab Anal,1998,12:378-382.
  • 4Kotajima N, Fukumura Y, Obata K, et al. The significance of determination of urinary type Ⅳ collagen concentrations from a random urine collection in patients with non insulin dependent diabetes mellitus. Rinsho Byori, 1998,46 : 277-282.
  • 5Gilber RE, Cox A, Wu L, et al. Expression of transforming growth factor-β1 and type Ⅳ collagen in the renal tubulointerstitium in experimental diabetes. Effects of ACE inhibition. Diabetes, 1998,47:414-422.

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