| BackgroundDiabetic nephropathy(DN) is one of the most important microvascularcomplications of diabetes and one of the leading causes of end stage renal diseases.Prevention or delay of DN development has become the hot point of diabetic research.Diabetic nephropathy is a kind of glomerulosclerosis charectarized by the diffuse glomerular hypertrophy,the thicken base membrane and progressive expansion of extracellular matrix in mesangium.The pathogenesis of DN is a synthetic result initiated by hyperglycemia or disorders of lipid metabolism and many factors including vascular active substances ,growth factors, cellular intermediator and chemotactic factors are involved in . The increased expression oftransforming growth factor 3 1(TGF- P 1 )and synthesis of collagen in kidney are most important. Many basic research and clinical trials have proved that ACEI can inhibit TGF- P 1 expression, preventing or delaying the development of diabetic nephropathy. Pioglitazone belongs tothiazolidinedione(TZD), a new kind of antidiabetic agent, its major function is to enhance the sensitivity of peripheral tissues to insulin by activating peroxisome proliferator-activated receptor- -y(PPAR7). Experiments have proved that TZD has some protecting effect on kidney in diabetic rats, which can decrease the urinary protein excretion of diabetic rats.Whether pioglitazone has this kind of effect on kidney and its mechanism are unknown.ObjectiveEstablishing Streptozotozin induced diabetic rat model, investigating the TGF- 3 1 and IV-collagen protein expressions in kidneys of diabetic rats and the protecting effect of pioglitazone on diabetic kidney .Research design and Methods1.experimental animalsSprague-Dawley rats(n=74), weighing 160-200g,aged 3 months,were randomized to three group: (1) normal controls (group C n=18) (2)diabetic untreated rats (group D,n=28) were rendered diabetic by single intraperitoneally injection of Streptozotozin (70mg/kg body wt) , the levels of blood glucose were determined 48 h after the injection and the rats with blood glucose levels above 16.7mmol/L were used as diabetic rats. (3) diabetic rats treated with pioglitazone (group DP, n=28) After the confirmation of diabetic rats, they were administrated orally by pioglitazone 20mg/kg/d, giving Saline of the equal volume to the group C and group D. At the 2,4,8weeks, take 6 rats from each group resperately, collecting their urine, arterial blood and kidneys.62.Methods(1) The levels of blood glucose, serum creatinine, serum ALT, urinary creatinine were measured by autobiochemiassay. Blood C-peptide was measured by chemilurninescence.(2) Body weight, kidney weight, the hypertrophy index of kidney represented by ratio of kidney weight/body weight were determined at all time points.(3)Urinary albumin was measured by radioimmunoassay, the urinary albumin excretion was represented by the ratio of urinary albumin/urinary creatine( u g/mg).(4) Kidney morphology: routine HE and PAS staining. (5)The protein of TGF- P 1 and IV-collagen expression in kidney were detected by immunohistochemistry (ABC). Immunostaining was semiquantitated at 400 X magnification by using a scale of 0-4,and the average score of 20 randomly selected glomeruli was calculated. 3.statistical analysisResults were expressed as m'ean盨D ^c ?j).Comparisons among 3 groups were analyzed by one-way analysis of variance,followed by either LSD or Games-Howell multiple comparision test to evaluate statistical difference between 2 groups.P<0.05 is regarded as significant.Results(l)Blood glucose, creatinine,ALT and C-peptideBlood glucose levels of group D and group DP were significantly higher than that of group C (P<0.01).Blood glucose level of group DP was lower7than that of group D ,the difference was significant at 4 weeks(/><0.05).The levels of blood creatinine and ALT of group D and group DP were significantly higher than those of group C at 2 weeks(P<0.05).There was no signifi...
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