Research on the subsequence of pathological changes of glomerulus and renal tubules in rats with diabetic nephropathy and its significance

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Volume 12, Issue 03, 2004
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Abstract: 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

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