The Effects Of Nrf2-ARE Antioxidant Pathway And GSK-3β In Coronary Arterioscieotic Heart Disease

Background: Recent studies have suggested oxidative stress play a critical role in theinitiation and progression of coronary arterioscleotic heart disease. In the new views, thereare also myocardial cell division and proliferation in the process of coronary heart diseasemyocardial remodeling. How to effectively defend against oxidative stress and regulate cellcycle of myocardial cells are new ideas to treat coronary heart disease. Untill present,resveratrol and rosuvastatin are demonstrated with the exactly protective effects on coronaryarterioscleotic heart disease and in the field of molecular studies, it was found thatNrf2-ARE antioxidant pathway plays the crucial role in antioxidant stress. Glycogensynthase kinase3β(GSK-3β) is a regulator of cell cycle proteins, its activity can affectnumerous aspects of cell differentiation, proliferation, and apoptosis. In this study,apolipoprotein(ApoE) knockout mice fed a high-fat diet, then given by gastric lavage toresveratrol and rosuvastatin respectively. We observed comparatively the specimens ofcardiovascular damage and research the changes of Nrf2, total GSK-3β and phosphorylatedGSK-3β to further clarify the cardiovascular effects and molecular mechanisms ofresveratrol.Objective: To establish the protection models of resveratrol and rosuvastatin tocoronary arterioscleotic heart disease, and detect the activity of nuclear factor-erythroid2-related factor-2(Nrf2) and glycogen synthase kinase3β(GSK-3β) as to clear the the effectsof Nrf2-ARE antioxidant pathway and GSK-3β in coronary arterioscleotic heart disease.Methods: Thirty male apolipoprotein(ApoE) knockout mice of age8weeks wererandomly divided into three groups(n=10,for each), including high-fat diet control group,high-fat diet-received resveratrol groups and high-fat diet-received rosuvastatin groups.Other living environment of all groups was same. Mice of the three groups were measuredweight every7days and were sacrificed after13weeks. The pathological slides made bymice heart tissues were abserved the formation of atherosclerotic lesions and development ofcardiac remodeling. Western blotting assay was used to detect Nrf2, total GSK-3β andphosphorylated GSK-3β by microscopy. We selected glyceraldehyde-3-phosphatedehydrogenase(GAPDH) as internal reference when detect.Results: 1)Weight change: in comparison to the high-fat diet control group, a significant weightcontrol effect was abserved in high-fat diet-received resveratrol groups and high-fatdiet-received rosuvastatin groups.2)The pathological slides reveal: degree of aortic sclerosisand myocardial cells injury in high-fat diet-received resveratrol groups and high-fatdiet-received rosuvastatin groups are less than in the high-fat diet control group.3) All theresults of western blot are adjusted by GADPH. Total GSK-3β in the three groups has nosignificant difference; the gene expression of phosphorylated GSK-3β in high-fatdiet-received resveratrol groups was enhanced,but in high-fat diet-received rosuvastatingroups was decreased;the gene expression of Nrf2in high-fat diet-received resveratrolgroups and in high-fat diet-received rosuvastatin groups were higher than in the controlgroup, while no significant differences in the levels of Nrf2in high-fat diet-receivedresveratrol groups and in high-fat diet-received rosuvastatin groups（P>0.05）.Conclusion:1)These results demonstrate that high-fat diet can act as one of risk factors for coronaryartery disease.2)Resveratrol and rosuvastatin have effects on anti-atherosclerosis andprotection of myocardial cells.3)Resveratrol and rosuvastatin can both regulate the increaseddegree of weight caused by high-fat diet.4)The effects on anti-atherosclerosis and protectionof myocardial cells of resveratrol and rosuvastatin are probably via Nrf2-ARE molecularpathway.