| Objective:To investigate the influence of all-trans retinoic acid(ATRA) on the expression of angiotensin converting enzymes(ACE) and angiotensin converting enzymes2(ACE2) in diabetes Mellitus(DM)rats renal and to probe the pathogenesis and the efficacy of ATRA which inhibit renal fibrosis of diabetic nephropathy(DN).Methods:48 ones of 60 healthy cotemporary male Sprague-Dawle rats were chosen randomly. The diabetes rat models were established by intravenous injection of STZ(65mg/kg). 72 hours after treated, the diabetic rats with blood glucose levels?16.7mmol/L,other 12 ones of 60 rats receiving an injection of citrate buffer were used as controls. The rats were randomly divided into four groups:(1) normal control group(NC group);(2)diabetic control group(DM group, untreated);(3)diabetic group treated by ATRA of 20mg·kg-1 once daily by gavage(DM+ATRA group);(4)diabetic group treated by captopril of 20mg·kg-1 once daily by gavage(DM+CAP group). The treatment was lasted for 8 weeks or 12 weeks. Observed general case and weight daily.Sixteen and twelfth weeks later, only six rats in four groups were put to death randomly. Blood glucose(BG),blood urea nitrogen(BUN), serumcreatinine(Scr),urine creatinine(Ucr), 24 hours urinary protein(Ualb) were measured;index number of kidney hypertrophy(kidney weight/body weight, KW/BW), creatinine clearance(Ccr) were calculated. The structure and ultrastructure of the kidney were examined by light and electron microscopy. The protein or m RNA expressions of ACE and ACE2 were detected through immunohistochemistry or RT-QPCR respectively.Results:1. After STZ injection(65mg/kg) the blood glucose of the experimental rats were higher than 16.7mmol/l, and we successfully established the diabetic rats.2. The rats in DM group ate and drunk too much with much urine and thinness, but not in NC group. In contrast to the DM group, after ATRA intervention or CAP treatment, symptoms above have been improved.3. No significant differences of the level of blood glucose were found between DM group and DM+ATRA group or DM+CAP group(P>0.05), but were always higher than that in NC group(P<0.01).The index number of kidney hypertrophy(KW/BW)?BUN?Ccr and the 24 hurinary protein in DM+ATRA group and DM+CAP group decreased significantly as compared to DM group(P<0.05),but both higher than in NC group(P<0.05).4. HE stainings showed a normal glomerulus structure in NC group, progressive increases in both glomeruli volume and mesangium matrix in DM group?DM+ATRA group and DM+CAP group throughout the experiment period,but both in DM+ATRA group and DM+CAP group were alleviated as compared to DM group. Transmission electron microscope showed that renal GBM in DM+ATRA group and DM+CAP group was thinner than in DM group, but thicker than in NC group.5.In comparison with NG group, the m RNA and protein expression of ACE in DM group increased significantly; in comparison with DM group,the m RNA and protein expression of ACE in DM+ATRA group and DM+CAP group decreased significantly,the difference had statistic significance(P<0.05).In comparison with NG group, the m RNA and protein expression of ACE2 in DM group decreased significantly; in comparison with DM group,the m RNA and protein expression of ACE2 in DM+ATRA group and DM+CAP group increased significantly, the difference had statistic significance(P<0.05).Conclusions:1. The diabetic rats model were successfully established by intravenous injection of STZ.2. ATRA can ameliorate the renal function and reduce the pathological damage of kidney.3. ATRA can delay renal fibrosis and inhibit the progress of diabetic nephropathy in rats with diabetes mellitus,the mechanism may be correlated with balance ACE and ACE2 expression in ras in kidney tissues. |
PDF Full Text Request