Intervention Of The Mechanisms Of MiRNAs Involvement Of Toll-like Receptors4Immunifaction In ApoE(-/-)Mice

Objective:In this study, Research of ApoE (-/-) mice were investigated using medium-intensity aerobic exercise and simvastatin pharmaceutical intervened. To explore atherosclerosis and the immune signaling pathways regulation of non-coding mircoRNA genes repair injury to its vascular inflammation and the possible molecular mechanism.Methods:ApoE gene knockout and high fat and high cholesterol diet induced atherosclerosis in mice were divided into quiet groups, exercise groups, drug groups; regularly measured serum of total cholesterol, low density lipoprotein, high density lipoprotein to test experiment model; collection of collagenase digestion of vascular endothelial cells; ELISA assay of serum inflammations and hormone levels in vascular tissue; immune was used to detect TLR4pathway and pathway-related factor expression and endothelial cell EGF, TGF-β expression; RT-PCR detection of CRP, MCP-1expression; Real time QPCR microRNA detection of non-coding gene expression.Results:(1) HE staining:12weeks Guiet Group ApoE (-/-) mice showed obvious plaque tissue endothelial cells; the drug groups showed endothelial cell swelling and foamy surface, the exercise group were no more than organizational change.(2) The exercise groups and drug groups the serum of IL-6, TNF-a levels lower than the rest group (p<0.01), while IL-10levels increased (p<0.01). Aerobic exercise groups and drug groups vascular tissue ET1, Ang II levels were higher than the rest group (p<0.05).(3) Exercise and drug groups in the AS mice TLR4、NF-Kb expression in vascular tissue decreased (p<0.01), down a series of inflammatory cytokines and inflammation-related substances in gene transcription to promote the inflammatory response factor C-reactive protein CRP, vascular endothelial adhesion molecule expression of MCP-1decreased (p<0.05).(4) Exercise groups mice vascular endothelial cells EGF, TGF-β mRNA expression were increased (p<0.01).(5) Quantitative PCR shows:exercise and drug groups were miRNA-155、expression decreased (p<0.01),miRNA-146a, miRNA-126up regulation.(6) Using the doble-fluorescence report vector assay verified the miRNA-146a downregulated the TRAF6expression.Conclusion: (1) This study found that moderate intensity aerobic exercise and simvastatin drugs mediated Toll-like receptor4-mediated pathway, and down TLR4, TRAF6and NF-κb expressionwhile endothelial cells in culture and secretion of ET, the ApoE(-/-) AS vascular injury repaired.(2) Aerobic exercise mediated miRNA-146a inflammatory TLR4signaling pathway, maybe also directly activated miRNA-155and miRNA-126regulated the inflammatory process, inhibited inflammation vascular injury; to curb the development of atherosclerosis in ApoE(-/-) mice.