| Objective 1. To observe the relationship between TGF 1 and diabetic nephropathy in experimental rats;2.To explore the effects of angiotensin converting inhibitor(ACEI)-fosinopril and angiotensin II receptor antagonist(ATRA)-losartan on renal TGF 1 in diabetic rats and their renoprotective mechanism. Method Four groups of rats were studied: A group(n=5),normal control rats;B group(n=5), strephtozotocin induced diabetic rats;C group (n=5),diabetic rats treated with fosinopril(5mg/kg.d);D group (n=5), diabetic rats treated with losartan(10mg/kg.d).Blood glucose(by glucose oxidase) ,urinary excretion rates of albumin(by radioimmunoassy), TGF 1,and retinal-binding protein(RBP)(by ELISA) were measured at the lst,2nd,4th and 12th week ,as well as the expressions of TGF 1 protein (by histochemical staining) and TGF 1 mRNA (by quantitative RT-PCR) in renal cortex and the relative kidney (ratio between kidney weight and body weight) at the 4th and 12th week. Renal patholochanges of diabetic rats was observed by electron microscopes at the 4th and 12th week.Result 1 .At the 1 st week(no treatment given),the urinary excretion rates of albumin in B, C, D groups were similar to that in A group (P>0.05),but the urinary excretion rates of RBP and TGF 1 were significant higher than those in A group, especially the latter. At the 2nd,4th and 12th week, the urinary excretion rates of albumin , RBP, TGF 1 all increased in B group compared with those in A group (P<0.01),and rose further as the nephropathy progressed. And in C, D group, the urinary excretion rates of the three proteins also increased compared with those in A group (P<0.01),but decreased significantly compared with those in B group(P<0.01),and no difference between C, Dgroups. Urinary TGF β 1 level was highly correlation with the urinary Alb, RBP level and relative kidney weight(r=0.884 , P<0.01; r=0.942,P<0.01;r=0.754, P<0.01,respectively). 2. The expressions of TGF β1 protein in renal cortex in B group was much higher than that in other 3groups(P<0.01), fosinopril and losartan can inhibit the expression of TGF β1, but fosinopril had stronger inhibitory effect than losartan at the 4th week (P<0.05),but at the 12th week, both have the similar effects. 3. The expressions of TGF β1 mRNA in renal cortex in B group increased greatly compared with A group at 4th week[(9.258 0.154) vs (1.375 0.276) 106copies, 1 cDNA, P<0.01],and further increased at the 12th week[( 14.983 2.88 l)vs (1.702 0.822) 106copies,ul cDNA, P<0.01],but in C group, the expression decreased to almost 50% at the 4th, 12th week, in D group , the expression was 70% of that in B group (P<0.05) at the 4th week and 57% (P<0.05) at the 12th week. And the expression was decreased more in C group than that in D group at the 4th week(P<0.05) ,but was similar at the 12th week . 4.The electron microscopes results showed significant mesangial expansion, glomerular basement membrane thickening in B group,but these abnormal changes were alleviated to a certain extent in C, D groups . Conclusion The overexpression of TGF β1 protein and mRNA in renal cortex of diabetic rats may be one of the mechanisms of diabetic nephropathy;the urinay excretion rate of TGF β1 might be one early marker for predicting diabetic nephropathy and assessing its severity. Fosinopril and losartan can suppress the expressions of TGF β1 protein and mRNA in renal cortex ,alleviate the patholochanges in kidney, as well as he urinay excretion rates of TGF β1,Alb,RBP in diabetic rats, which suggest that the renoprotective effects of ACEI and ATRA may be partly due to their effects in down-regulating the TGF β1 production in renal cortex. |
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