| Objective and backgroundDiabetic nephropathy is a common and serious complication of diabetes mellitus. Many cytokines and growth factors are involved in the pathogenesis of diabetic nephropathy. Of these , transforming growth factor-beta(TGF- 3 ) has been suggested to play a key role in accumulation of extra cellular matrix in diabetes. Intervention of the activity of TGF-P seems to slow the progression of diabetic nephropathy. But ,up to now, we have not found a reliable method to detect the activity of TGF- P in diabetes. The usefulness of the determination of urinary TGF- ft excretion or serum TGF- 3 activity is controversial.As to prevention or treatment of diabetic nephropathy, intensive control of blood glucose and blocking rennin- angiotensin system (RAS) with Angiotensin converting enzyme inhibitors(ACEI) or Angiotensin IIreceptor antagonists are important. Thiazolidinedion (TZD) compounds, novel insulin-sensitizing agents, are found to ameliorate albuminuria both in diabetic models and patients, but the exact mechanism remains to be clarified.The current study was to investigate TGF~PImRNA levels in renal cortex and glomerular dysfunction of STZ-induced diabetic rats, andthe effect of pioglitazone on them; And also to examine the relation of TGF-0 ImRNA levels between the renal cortex and peripheral blood mononuclear cells (PBMC) of diabetic rats . Research design and Methods54 Sprague-Dawley rats weighing 160~200g were randomly divided into three groups: 18 normal control rats (group C), 18 diabetic rats (group D) and 18 diabetic rats treated with pioglitazone (group DP). Rats of group D and group DP were made diabetic by a single intraperitoneal injection of STZ in a dose of 70 mg. kg body. The levels of blood glucose were determined 2 days after the injection of STZ, and the rats with blood glucose leve 16. 7mmol/L were determined as diabetic rats. Pioglitazone was orally administered to rats of group DP by a gastric tube at a dose of 20mg. kg1, d from 3 days after STZ injection; Six rats from each group were sacrificed at 2,4 and 8 weeks. Spot urine samples were collected for measurement of albumin / creatinine ratios and blood samples were collected from femoral arteries for extracting PBMC and measurement of glucose levels, C peptide concentrations and ALT levels. After death, kidneys were removed, weighed and dissected to separate the cortices for total RNA isolating. Total RNA of the renal cortex and PBMC were isolated with TRIzol Reagent. TGF- 0 ImRNA levels of renal cortex and PBMC were examined by RT- PCR +Slit hybridization analysis. Results1. The blood glucose levels of group D and group DP were significantly higher than those of group C at 2, 4,8 weeks (P<0. 001);C peptide concentrations of group D and group DP were significantly lower than those of group C at all time points (P<0. 05). Pioglitazone had no effect on blood glucose and C peptide in diabetic rats except at 4 weeks.2. Body weight of group D and group DP were lower than those of group C at 4, 8 weeks (P<0. 05); Kidney weight of group D and group DP were higher than those of group C at 8 weeks (P<0. 05); Kidney hypertrophy indexes (taken as kidey /body weight) of group D and group DP were higher than those of group C at each time point (P<0. 05).3. The values of albumine / creatinine (A/C) of group D were slightly higher than those of group C at 2,4,8 weeks (P>0.05); Pioglitazone could slightly reduce A/C at all time points (P>0. 05).4. TGF- P ImRNA levels in renal cortexes of group D increasedmarkedly compared with those of group C at 2 weeks (0. 731 ?.173 VS0. 459?. 05, P<0. 05), which was sustained at 4,8 weeks (P<0. 05);Pioglitazone significantly inhibited the increased levels of TGF-PImRNA in renal cortex at each time point (P<0. 05).5. TGF-P ImRNA levels in PBMC of group D were slightly higher than those of group C (P=0.14) at 4 weeks; At 8 weeks, the difference became significant (P=0. 01); Pioglitazone had no significant effect on TGF-0 ImRNA levels in PBMC of diabetic...
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