Atorvastatin Regulates The Polarization And NGF Expression Of Mouse RAW264.7 Macrophages By SIRT1

BackgroundThe pathology of myocardial infarction is the hallmark of coronary artery occlusion,leading to myocardial ischemia.Ischemic conditions damage myocardial tissues,while necrosis of cardiomyocytes initiates inflammatory reactions.Myocardial infarction(MI)is a common cardiovascular disease in clinical practice and the leading cause of cardiovascular death worldwide.Upon myocardial infarction,circulating blood monocytes rapidly infiltrate into the injured myocardium and differentiate into macrophages.As the main immune cells,macrophages exhibit two major phenotypes:classically-activated M1 macrophages and alternatively activated M2 macrophages and play multiple roles in myocardial injury and wound healing.Nerve growth factor(NGF)can reduce inflammatory response.Macrophages participate in the entire inflammatory response process by regulating the expression of nerve growth factor(NGF).Statins are very effective and safe for primary prevention of cardiovascular events,and can reduce the occurrence of cardiovascular and cerebrovascular events.Silence information regulator 1(SIRT1)is a NAD+-dependent histone deacetylase that is closely related to cell differentiation,aging,apoptosis and energy metabolism,and plays a protective role in cardiovascular events.At present,drugs can affect macrophage polarization by up-regulatingzSIRT1,but whether atorvastatin can increase SIRT1 expression can affect macrophage polarization has not been reported.ObjectiveThe purpose of this study was to investigate the anti-inflammatory mechanism of atorvastatin through the intervention of atorvastatin in the phenotype transformation of macrophages in mice and its effect on NGF,so as to provide a new direction for the follow-up study on the mechanism of post-mi sympathetic nerve.MethodsRAW264.7 cells were incubated with high glucose DMEM for 24 h.RAW264.7 cells were stimulated with lipopolysaccharide(LPS)+interferon-y(IFN-y)to induce Ml polarization,and RAW264.7 cells were stimulated with interleukin-4(IL-4)+interleukin-13(IL-13)to induce M2 polarization and then intervened with Atorvastatin.All cells were divided into control group(intervened only with Dimethyl sulfoxide),Ml group(LPS+IFN-y stimulated RAW264.7 cells),M2 group(IL-4/IL-13 intervened RAW264.7 cells),M1+A group(M1 group cells were intervened with Atorvastatin)and M2+A group(M2 groupcells were intervened Atorvastatin).The phenotype of macrophage polarization was analyzed by flow cytometry.Western blotting was used to detect the protein expression of SIRT1 and NGF.The levels of interleukin-1?(IL-1?)and tumor necrosis factor(TNF-?)were detected by enzyme-linked immunosorbent assayResultsThe relative expression of SIRT1 in M1 group and M2 group were significantly lower than that in control group(P<0.05),the relative expression of SIRT1 in M1+A group and M2+A group increased significantly(P<0.05).The relative expression of NGF in M1 group and M2 group were significantlyhigher than that in control group(P<0.05),and the relative expression of NGF in M1 group was significantly higher than that in M2 group(P<0.05).However,the relative expression of NGF in M1+A group and M2+A group decreased significantly(P<0.05),and the decrease in M1+A group was greater than that in M2+A group(P<0.05).The secretion of IL-1? and TNF-? in M2 group and M1 group were significantly higher than those in control group(P<0.05).The secretion of IL-1? and TNF-?in M1+A group and M2+A group decreased,however,the secretion of IL-1? and TNF-? in M1+A group were significantly lower than those in M2+A group(P<0.05)ConclusionAtorvastatin regulates the phenotypic transformation of macrophages by upregulating SIRT1,regulates the expression of NGF,and reduces the release of inflammatory factors such as TNF-?,IL-1? and so on.