Research On Relationship Between Vascular Calcification And Hyperlipidmia, And Interfered With Simvastatin In Vivo And Vitro On Rat

Objective Vascular Calcification and Hyperlipidmia were dangerous factor of health in human being. To explore relationship between hyperlipidmia and vascular calcification and possible mechanism by developing animal models involved in vivo and vitro, and interfering with simvastatin. Methods Vascular calcific model were induced by vitamin D3 intramuscular injection and nicotine (P.O), Hyperlipidmia model were induced by high diet,and rats calcific and high lipid vascular smooth muscular cells (VSMCs) were induced byβ-glycerophosphate and mevalonate .The total aorta Ca²⁺ content in aorta and VSMCs were measured by atom absorptive spectrophotography; the alkaline phosphatase (ALP) activity in plasma, aorta and VSMCs were determined by the use of phenyl diphosphate-2-sodium; and the levels of osteocalcin, endothelin in plasma and aorta were determined by radioimmunoassay. Total cholesterol, high-density lipoprotein cholesterol, superoxide dismutase, maleic diadehyde and total anti-oxidation in plasma were determined by enzymatic method. Results Vitamin D3 and nicotine induced vascular calcification in rats andβ-glycerophosphate induced calcification in VSMCs too. With increase in the total Ca²⁺ content and ALP activity in aorta and VSMCs, and osteocalcin level in plasma and aorta. High diet induced hyperlipidmia and mevalonate induced hyper lipid in VSMCs too, with increase in the total cholesterol and decrease in the high-density lipoprotein cholesterol in plasma. TC, ALP, OC and total Ca²⁺ content were increased with high diet based on vascular calcification than vascular calcification group and hyperlipidmia simply. The total aorta Ca²⁺ contents were less by 12.84% and 13.94% in aorta and VSMCs, ALP activity less by 11.33% , 35.89% and 32 % in plasma, aorta and VSMCs, OC level were less by 11.33% , and 35.89% in plasma and aorta after treated with simvastatin in vascular calcification group. The total aorta Ca²⁺ contents were less by 32.67% and 46.78% in aorta and VSMCs, ALP activity less by 34.55% , 30.82% and 35.69% in plasma, aorta and VSMCs, OC level were less by 24.67% and 41.43% in plasma and aorta after treated with simvastatin in vascular calcification group based on high fat. Moreover, MDA and endothelin were increased , SOD and total anti-oxidation were decreased in calcification group and hyperlipidmia group , especially in vascular calcification group based on high fat. However, MDA and endothelin were decreased , SOD and total anti-oxidation were increased after treated with simvastatin respectively. Conclusions Our results indicated that hyperlipidmia can significantly accelerate vascular calcification . Simvastatin can significantly attenuate the calcification during decreasing cholesterol through the antagonism with endothelin system and the balance with oxidation/anti-oxidation in plasma or cells.