Atorvastatin-induced Atherosclerotic Vascular Smooth Muscle Cell Apoptosis And Its Impact On Bkca Expression And ERK Signaling Pathways

Background：Proliferation and apoptosis imbalance of vascularsmooth muscle cells plays an important role in thedevelopment of atherosclerosis. Large conductancecalcium-activated potassium channels(BKca), extracellularsignal-regulated kinase (ERK) signaling pathway are consideredinvolved in the apoptosis regulation of smooth muscle.Atorvastatin-induced apoptosis of vascular smooth muscle isone of the anti-atherosclerotic mechanisms, whether it wasby regulating BKca expression and ERK signaling pathwaysto achieve, and what is their relationship have not beenfully elucidated.Objective: To investigate whether atorvastatin induct VSMCapoptosis by the expression of BKca and ERK signalingpathways.Methods:20rabbits were randomly divided into normaldiet group (NOR group, n=8), atherosclerosis group (AS group, n=6) and atorvastatin group (AVT group, n=6),16weeks, buildingrabbit model of atherosclerosis. By HE staining ofatherosclerotic lesions, in situ nick end labeling (TUNEL)detecte VSMC apoptosis, apoptotic index (apoptosis index, AI); situhybridization (ISH) method to detect rabbi t expression ofthoracic artery BKca β subunit mRNA KCMB1gene; usingWestern blots (Western Blot) assay phosphorylated changes ofextracellular signal-regulated kinase1/2(p-ERK1/2).Results1. As HE staining showed establishment of rabbitatherosclerotic model in group AS neointimal hyperplasiasignificantly thicker,presenting typical atherosclerotic lesions, Thereis a clear difference compare with the normal group andatorvastatin group;2. PCNA expression AS group and AT group ’s PCNA positive expression were highe r than the normal group, while the AT group ’s positive expression rate wasless than AS group ’s (P <0.01);3. TUNEL assay of apoptosis, AI ofAS group was27.8±1.36%, significantly higher than thenormal group (AI was6.8±1.08, P <0.01); AI of atorvastatin groupwas36.5±1.53%, significantly higher than the AS group (P<0.01);4.ISH detection of visible expression of AS groupKCNMB1gene mRNA (gray value147±5.8) than the normalgroup (gray value105±5.5, the lower the value of the gray value, whichmeans that the higher the expression) was significantly lower (P <0.01);mRNA expression of atorvastatin group (gray value of116±6.9)was significantly increased than the AS group (P <0.01);4.Western blot (western blot) to detect the expression ofp-ERK1/2positive expression rate of AVT group is lowerthan the AS group(p＜0.01).Conclusion Atorvastatin induced apoptosis of VSMC maybeby upregulating the expression of BKca KCNMB1gene ’smRNA and inhibiting ERK signaling pathway of these twoindependent mechanismsto.