Protective Effects Of High-dose Vitamin D Injection On Injury In Streptozotocin-induced Diabetic Mice

Objective: To study the protective effects of high-dose vitamin D injection on injury in streptozotocin-induced diabetic miceMethods: The study was designed into three parts: First, to establish a mouse model of diabetes mellitus(DM). Second, to investigate the impact of vitamin D intervention on the kidneys of diabetic mice; Third, to find out what is the role of vitamin D play in those diabetic mice which have a low-dose cadmium exposure.(1)The model was established by intraperitoneally given low-dose streptozotocin(40mg/kg, STZ), The mice were injected intraperitoneally once a day, continuous injected for five days.(2) The mice were detected fasting blood glucose(FBG) after 72 hours of the last injection, those with a higher FBG than 10mmmol/l were considered successful models of diabetic mice.(3) The diabetic mice were randomly divided into five groups: model control group, high-dose vitamin D group(1000IU/w, intramuscular injection once a week), CdCl2 intervention group(1mg/kg,twice weekly), VD + CdCl2 group, positive control group(losartan, 0.025 mg /ml), while setting up a control group with normal mice at the same time. The mice were continuously administrated for 4 weeks, in the same time, the general situations in mice were observed,and body weight,food intake,water intake, blood index(fasting glucose)were regularly tested. After four weeks’ treatment, by using the metabolism and activity monitoring system to collect the data of activity, food intake, water intake. At last, body weight, organ weight, organ index, urine index( urine sugar and urine protein), blood index( fasting glucose, creatinine, urea) were tested, while the examination of kidney histopathology was carried out.Results:(1)The diabetic mice groups’ fasting glucose was significantly higher than the control group. The increasing body weight between diabetic mice groups and the control group was significantly different. The kidney coefficient and liver coefficient of diabetic mice was statistically significant escalation in contrast with the control group. After theintervention of vitamin D, the mice acquired a better physical activity compared with the model control group. Compared with model control group, urinary protein and creatinine ratio decreased significantly. In model control group, the number of glomerular cells have increased, some renal proximal tubular epithelial cells disordered, part of renal tubular epithelial cells have mortified and swelled in the kidney tubular occured transparent tube and shedding phenomena. And these phenomenons have been ameliorated after vitamin D intervention.(2) After the injection of cadmium, the spleen coefficient and liver coefficient was significantly increased than the control group, and water intake was also significantly increased than the control group. Vitamin D had no significant effect on fasting blood,body weight in those diabetic mice which have a low-dose cadmium exposure. There was no significant difference in urinary protein and creatinine ratio between CdCl2 alone intervention group and VD + CdCl2 group.CdCl2 alone intervention group had a lower activity than VD + CdCl2 group. Compared with CdCl2 alone intervention, Vitamin D and CdCl2 joint intervention have significantly improved the renal tubular epithelial cells shedding, necrosis. Vitamin D ameliorated cadmium-induced alterations in diabetic mice.Conclusions:1, Compared with the control group, the fasting blood glucose was significantly higher than the control group. And high-dose of vitamin D intervention have no significant impacton fasting glucose.2,High-dose of vitamin D intervention significantlyimproved physical activity in diabetic mice and reduced the urine protein and creatinine ratio. Combined with the slice results, it suggests that vitamin D significantly ameliorates the renal injury in diabetic mice.3,Vitamin D ameliorated low dose cadmium-induced alterations in diabetic mice.