The Effects Of Hyperhomocysteineamia And Hyperinsulinism On Human Vascular Endothelial Cells On The Expression Of TM

Objective:To investigate HUVEC injury as a result of high exogenous hyperinsulinism and hyperhomocysteineamia and to explore the intervention effect of rosiglitazone and to find its mechanism.Methods:1.After the ceils were cultured to 96 holes on the board,endothelial cells were incubated in the RPMI-1640 culture medium mixed with different concentrations of insulin or different concentrations of homocysteine separately for 24h,48h,72h.Then we observe cell growth status by inverted microscope,determined cell number and function by MTT.2.According to MTT results,we select the appropriate concentration to group and use a certain concentration of rosiglitazone to intervene.These groups were the control group,injury groups(high Hcy group,high-Ins group,high Hcy + high Ins group)and drug intervention groups(high Hcy + Ros groups,high-Ins + Ros groups,high Hcy +high Ins + Ros groups). Endothelial cells were incubated for a certain period of time,we observed cell growth status, determinated the level of malondialdehyde(MDA) in cell culture supernatant,detected superoxide dismutase(SOD) in cell culture supernatant,and determinated TM levels in cell culture supernatant.Results:1.Physiological concentrations and low concentrations of insulin can promote the proliferation of endothelial cell,and there was a peak,more than a certain concentration of insulin inhibited cell growth dose-dependently and time-dependently.Inhibition of cell growth was not obvious by low concentrations of homocysteine.As the concentration and time increased,cell growth were inhibited more obviously.2.High concentrations of insulin and or high concentrations of homocysteine caused cell injury and the expression of SOD,MDA,TM increased.Cell injury of high insulin and high homocysteine mixed culture were more obvious than the injury of the corresponding pure cultivate and the expression of SOD,MDA and TM increased significantly.3.Rosiglitazone can weaken the injury of endothelial cell of high concentrations of insulin and high concentrations of homocysteine and the mixed culture,SOD,MDA and TM did not change more.Conclusions: 1.The function of Insulin for endothelial cells are biphasic.Physiological concentrations and low concentrations of insulin can promote the proliferation of endothelial cells,directly produce the protective effect on the vascular endothelial cells and promote the repair of vascular endothelium,therefore the formation of atherosclerosis was resisted,dose-and time-dependently.2.High insulin and high homocysteine may damage endothelial cells and inhibit cell growth, and the expression of injury markers MDA,TM increased and SOD decreased.There is synergy between High insulin and high homocysteine and promote atherosclerosis and diabetic vascular complications development more rapidly.3.Rosiglitazone have antagonistic role on the injury of endothelial cell which may be moderate to be postponed the occurrence and development of diabetic angiopathy.