Telmisartan's Intervention Role On Diabetic Kidney Disease And Influence On Expression Of TypeⅠInositol 1,4,5-Triphosphate Receptor

Background and ObjectivesDiabetic kidney disease (DKD) is one of long-term complications of diabetes mellitus and the major cause of end-stage renal disease. The mechanisms of DKD have not been comprehensively reviewed till now. The IP3 is a transmembrane protein. After IP3 combines with IP3 receptor, the calcium chanel opens. The Ca2+ accesses in cytoplasm from endoplasmic reticulum, and adjust cytokine, regulatory factor, and effector, and participate biophysical profile in cells. The experiment had induced the rat model of diabetic kidney disease by streptozotocin(STZ), and intervention with Telmisartan(ARB). Through observating the rats biochemical indicator and the allocation of IP3R-I on the kidney,expressing circumstance of IP3R mRNA, It were comprehend that the effect of IP3R-I in the mechanisms of diabetic kidney disease.Methods30 SD rats were randomly assigned to following groups:normal control group (C, n=10), model group without Telmisartan (D, n=10), model group with Telmisartan (T, n=10). After fasting 12 hours,the rats of Dgroup and T group were injected single dose STZ in 0.1 mol/1 citrate buffer, pH 4.5 (60mg/kg), the rats of and C group were injected citrate buffer.3 days after injection, blood glucose levels were determined, and＞16.7mmol/l were succeed.After 3 weeks, collecting the urine protein of 24 hours through metal metabolism cages, and measuring urinary protein of 24 hours by Sulfosalicylic acid method. The rats of urine protein of 24 hours >30mg were succeed. The rats of T group were given Telmisartan suspension in 40mg-kg-1·d-1,and the others were given distillated water. After 8 weeks, collecting the rats, and measuring body weight. At the end of procedure, blood samples were collected for analysis of whole blood glucose, serum creatinine, urea nitrogen; 24 hours urine were collected for quantity of 24 hours urinary protein. Kidney were harvested for histological and immunohistochemistry analysis. HE staining and Masson staining were performed, through RT-PCR meature expressing of IP3R-I on the mesangial cell and vascular smooth muscle cell, with mRNA changing condition.ResultsAt the 8 weeks after operation,1. The blood sugar of normal control group, model group without Telmisartan,model group with Telmisartan were 5.08±0.86, 18.33±0.8,8.7±1.26, and there were significant difference between groups(P＜0.05); The serum creatinine were 60.13±6.55,82.50±9.63,76.63±7.59, and there were significant difference between groups(P＜0.05); The albumin were 38.15±1.52, 23.62±0.87,31.92±0.96, and there were significant difference between groups(P＜0.05); The serum cholesterol were 1.04±0.12,1.48±0.16,1.23±0.09, and there were significant difference between groups(P＜0.05); The triglyceride were 0.50±0.08, 0.96±0.07,0.72±0.06, and there were significant difference between groups(P＜0.05); The 24 hours urinary protein were 18.06±2.25,76.50±13.26,28.72±14.35, and there were significant difference between groups(P＜0.05); The kidney weight index(kidney weight/body weight) were 3.26±0.47,3.78±0.28,3.62±0.33, and there were significant difference between groups(P＜0.05).2.Immunohistochemistry staining showed typeⅠIP3R mainly distributed in the cytoplasm of glomerular cslls and vascular smooth muscle cells.The percentage of positive cells in immunohistochemistry staining of groups were 24%±3%,65%±5%,43%±4%, and there were significant difference between groups(P＜0.05).3. The results of RT-PCR showed:the gray scale of groups were 0.38±0.03,0.75±0.08,0.61±0.05, and there were significant difference between groups(P<0.05).conclusionIP3R-Ⅰresided in the Mesangial cell and vascular smooth muscle cell. IP3R-Ⅰexpressing became augment in the Mesangial cell and vascular smooth muscle cell when there was DKD. The Telmisartan could reduce IP3R-Ⅰexpressing in the kidney and improve urine protein,biochemical markers, and delay end-stage renal disease.