The Clinical And Pharmacology Study Of Cardiology Disease On Insulin Resistance

Background and purpose:Insulin resistance is a common cause of metabolic syndrome including coronary heartdisease and diabetes, it is now considered the "common soil" leading to metabolicsyndrome. A number of coronary heart disease, especially patients with acute coronarysyndrome, there are varying degrees of insulin resistance, clinical advocates the applicationof high-dose statin treatment in order to improve treatment outcomes, but there is still a lackof theoretical basis and experimental basis in this respect, this is also the subject of one ofthe research basis points. Our group has been successfully carried out animal model to thestudy of the mechanism of insulin resistance and atherosclerosis, and achieved fruitfulresults. More in-depth study of the cell model of insulin resistance atherosclerosisexperiment has not yet commenced, this is also another basis points of this topic. This studywas to observe the acute myocardial infarction in patients with insulin resistance andmacrovascular disease status, and with cell culture technology to create an insulin resistancein vascular endothelial cell model to study the mechanism of insulin resistance in endothelialcells, to study insulin resistance endothelial cells led to the mechanism of atherosclerosis,further study of the corresponding drugs such as atorvastatin statins such as insulinresistance, endothelial cells and mechanism of action against endothelial cells inatherosclerosis. More in-depth research laid the experimental basis for future application ofthe insulin resistance model.Methods:We used atorvastatin as the study drug, built up endothelial cells insulin resistancemodel through cell culture, observed endothelial cells with morphological observation,detected nitric oxide content with Nitroreductase Determination; detected endothelin levelswith radioimmunoassay determination; the use of laser copolymer gel and western blotmethod to observe the nitric oxide synthase expression and quantitative analysis. In thisstudy, NO, ET-1and eNOS are research indicators of acute myocardial infarction inperipheral blood of patients with endothelial nitric oxide synthase, such as insulin resistanceand macrovascular disease.Results: 1.I observed insulin resistance model in low sugar medium, I found that10-4insulin/30mM glucose/1μM dexamethasone for48h had the least glucose consumed amount (P<0.05), was the optimal dose for the model.2.I observed insulin resistance model in high sugar medium, I found that10-3insulin/30mM glucose/1μM dexamethasone for48h had the least glucose consumedamount (P <0.05), was the optimal dose for the model.3.Atorvastatin of ECV cells;103-10-4umol/L after24h of drugs on glucose content wasno significant difference (P>0.05), suggesting that the drug had not significant effect onnormal cells glucose consumption.4.Atorvastatin on insulin resistance in the protective effect of ECV cells;103-10-4umol/L after24h of drugs on glucose content was significant difference (P<0.05)., suggestingthat the drug had significant effect on normal cells glucose consumption. MTT values hadnot significant difference (P>0.05), suggesting that the drug effects on insulin resistancemodel does not cause cell proliferation, does not interfere with the results.5.Atorvastatin on the EC cell NO secretion: drugs acting on insulin resistanceinendothelial cells after24hours, the ET-1were significantly lower and NO were higher(P <0.05), prompted drug significantly to improve the role of insulin resistancein endothelial cells.6.We found that atorvastatin improve insulin resistance, the optimum concentration ofatovastatin is10-3mmol/L.7.Atovastatin on the EC cell eNOS activety: drugs acting on insulin resistance inendothelial cells after24h compared with the controle group, atovastatin were significantlyincreased eNOS levels in the cells(P<0.05), suggesting that atovastatin improve insulinresistance by improving eNOS activity.8.Atovastatin on the EC cells PI-3K pathway: drugs acting on insulin resistance inendothelial cells after24h, with the control group phase atarvastatin can be significantincrease of PI-3K content(P<0.05), suggesting that atovastatin improve endothelial cell byPI-3K pathway.9.the expression of eNOS in peripheral blood of patients with AMI was reduced bydown-regulating nitric oxide (NO) levels and increase of ET-1levels involved in theoccurrence and development of IR and vascular disease.Conclusion:1.Successfully established a model of insulin resistance in endothelial cells; 2.Determine the optimal concentration of the drug for insulin resistance in endothelialcells;3. Atorvastatin can significantly improve the content of nitric oxide in endothelial cells,thus helping protect endothelial cells against the role of atherosclerosis;4. Cells to secrete NO significantly decreased insulin resistance was negativelycorrelated with the glucose content of the medium; NO and ET-1was negatively correlated;NO and glucose was negatively correlated;ET-1was positively correlated with glucose. Tipof NO and ET-1is a mutual restraint factors to participate in the mechanism of endothelialfunctions;5. Atovastatin can significantly improve endothelial functions in endothelial cells, itsmechanism and eNOS levels in order to produce more NO;6. Atorvastatin by increasing the content of PI-3K in insulin resistance in endothelialcells involved in the metabolism of insulin, improved endothelial functions by the PI-3Kpathway;7. Atovastatin can protect endothelial function directly;8.The expression of eNOS in peripheral blood of patients with AMI was reduced bydown-regulating nitric oxide (NO) levels and increase of ET-1levels involved in theoccurrence and development of IR and vascular disease.