The High Calcium Diet On Experimental Diabetic Nephropathy In Rats Tissue Calcification

Diabetes Mellitus is the leading cause of end-stage renal failure (ESRF).The increasingly risk of cardiovascular disease (CVD) mortality in adult patients with ESRD is 10 to 100 times higher than that of the non-ESRD patients. 13.1% of newpatients to dialysis had diabetes as their cause of ESRD in 1980. In 2002, 43% to 64% of individuals (range because of differences in race/ethnicity) have diabetes as their cause of ESRD, and 59% of all patients beginning dialysis have diabetes as a primary or secondary diagnosis. Hyper -tension is found in the majority of individuals at the start of dialysis. The population is also older. Coronary artery calcifica -tion is very common in dialysis patients. Depending on the age of the patient population examined, 54% to 100% (mean 83%) of dialysis patients in case series have some degree of coronary artery calcification, with scores markedly above the general population. More than half the death in patients with ESRD are due to cardiovascular disease. Vascular calcification (VC) commonly seen with CVD is independent prognostic marker of CVD morbility and mortality in patients with ESRD. Vascular calcification is currently considered an cell-mediated and actively regulated process that like bone formation with phenotypic transition of vascular smooth muscle cells(VSMC). vascular smooth muscle cells in the process of mineralization undergo a phenotypic transition toward an osteogenic phenotype. Core binding factor alpha l(CBFAl) is an osteoblast-specific transcription factor required for osteoblast differentiation and earliest specific marker. Osteocalcin is noncollagen protein in bone tissue and advanced staged marker of mature osteoblast.It conteins three γ -carboxyglutantic acid residues.It is shown that elvated calcium orphsphote directly affect on human or bovine VSMCs and promote mineralization in vitro.A little data about this present in vivo.Using experimental diabetic nephropathy modle rats by unique nephrectomized and STZ-induceded,this study compare high calcium diet and low calcium diet affecting on among mineral metabolism, vascular calcification and CBFA1. Non-diabetes sham operation rats serves as control groups. Experimental rars was classified to four groups:① DS (diabetes sham operation );②DS-HC (diabetes sham operation+high calcium ); ③ DUN (diabetes unilater nephrectomized );④DUN-HC (diabetes unilater nephrectomized + high calcium ); ⑤ NS (non-diabetes sham operation).Experimental rars underwent one of the foliowong treatments for 6 months:① or ③ was fed with high phosphate and low calcium. ②,④and⑤ was fed with high phosphate and high calcium.Appropriate blood,urine,and kidney tissue samples were taken at six months. CBFAl expression was investigated using immunohistochemistry and Western blotting at 6 months. Osterocalcin (BGP) was investigated by immunohistochemistry at 24 weeks, calcium , phosphate,renal function and parathyroid hormone was examined respectively. Calcium deposition of vessle and kidney tissue was investigated using Von Kossa staining. There was no statistic significance among blood sugar,body weight,kidney weight and urinary volume in groups of diabetic rats.There was significantly reduce compare NS groups with diabetic rats in blood sugar,body weight,kidney weight and urinary volume. DUN blood calcium was the lowest among the other groups and was significance compare with the othrs groups.DUN had higher parathyroid hormone level than the other groups's.There ware significantly difference between groups.the 24 hour urinary protein excretion in DUN was significantly higher than theother groups. The immunohistochemistry expression level of CBFA1 or BGP in kidney and vascular tissue was higher in DUN than the other groups.There was no expression of CBFA1 and BGP in NS. high calcium intake decreases blood urea nitrogen and serum creatinine, suppresses plasma parathyroid hormone(PTH) and phosphate level, reduces vascularity and kidney calcification.The extent of calcium salte deposition is positive corelation to the expression of CBFAl or BGP and to the level of serum cretinine,PTH and 24 hour urinary protein, the expression of CBFAl or BGP is nigetive corelation to the serum calcium level. The precise mechanism of tissue calcification is to be further study.