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首页|期刊导航|针刺研究|艾灸对ApoE-/-动脉粥样硬化小鼠SIRT1/FOXO3a信号通路的影响

艾灸对ApoE-/-动脉粥样硬化小鼠SIRT1/FOXO3a信号通路的影响OA北大核心CSTPCDMEDLINE

Effect of moxibustion on the SIRT1/FOXO3a signaling pathway in ApoE-/-mice with atherosclerosis

中文摘要英文摘要

目的:观察艾灸对ApoE-/-动脉粥样硬化(AS)小鼠血脂代谢、胸主动脉病理形态及胸主动脉沉默信息调节因子1(SIRT1)/叉头框转录因子O3a(FOXO3a)通路分子表达的影响,探讨艾灸防治AS的潜在机制.方法:10只C57BL/6J小鼠予普通饲料喂养设为对照组,30只ApoE-/-小鼠饲喂高脂饲料复制AS模型,随机分为模型组、辛伐他汀组和艾灸组,每组10只.于造模第1天对各组小鼠进行干预,艾灸组小鼠于"膻中""神阙"、双侧"内关""血海"处行温和灸治疗,每日1次,每次30 min,每周连续5次,干预12周.辛伐他汀组予辛伐他汀灌胃(2.5 mg·kg-1·d-1),每日1次,每周连续5次,干预12周.干预期间观察记录小鼠的体质量及一般情况;干预结束后,采用全自动生化分析仪检测小鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量;HE染色观察小鼠胸主动脉病理形态;ELISA法检测小鼠血清ox-LDL含量及SOD活性;Western blot法及实时荧光定量PCR法分别检测胸主动脉SIRT1和FOXO3a蛋白及mRNA的表达水平.结果:与对照组比较,模型组小鼠第 8周、第 12周的体质量,血清TC、TG、LDL-C、ox-LDL含量显著升高(P<0.05,P<0.01),HDL-C含量、SOD活性、胸主动脉SIRT1蛋白及mRNA表达量显著降低(P<0.05,P<0.01);HE染色显示胸主动脉血管内膜增厚,内皮细胞变性、肿胀和脱落.与模型组比较,辛伐他汀组及艾灸组小鼠第8周、第12周的体质量,血清TC、TG、LDL-C、ox-LDL含量显著降低(P<0.01),血清SOD活性、胸主动脉SIRT1蛋白及mRNA表达显著升高(P<0.01),辛伐他汀组HDL-C含量显著升高(P<0.05);两组胸主动脉结构较为完整,管腔较为规则,中膜内弹性膜排列较为整齐,内膜可见少量的内皮细胞变性和肿胀.与辛伐他汀组比较,艾灸组各指标差异均无统计学意义;胸主动脉病理结构变化大致相同.结论:艾灸可以降低AS模型小鼠的体质量,调节血脂水平,并修复血管内膜,减轻内皮损伤,其作用机制可能与调节SIRT1/FOXO3a信号通路改善氧化损伤相关.

Objective To observe the effects of moxibustion on blood lipid metabolism,pathological morphology of thoracic aorta,and the expression of silent information regulator 1(SIRT1)and forkhead box transcription factor O3a(FOXO3a)in ApoE-/-atherosclerosis(AS)mice,so as to explore the potential mechanism of moxibustion in preventing and treating AS.Methods Ten C57BL/6J mice were fed a normal diet as the control group,and 30 ApoE-/-mice were fed a high-fat diet to establish the AS model,which were randomly divided into the model group,simvastatin group,and moxibustion group,with 10 mice in each group.From the first day of modeling,mice in the moxibustion group received mild moxibustion treatment at"Shenque"(CV8),"Yinlingquan"(SP9),bilateral"Neiguan"(PC6)and"Xuehai"(SP10)for 30 min per time;the mice in the simvastatin group were given simvastatin orally(2.5 mg·kg-1·d-1),with both treatments given once daily,5 times a week,with a total intervention period of 12 weeks.The body weight and general condition of the mice were observed and recorded during the intervention period.After the intervention,the contents of serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using an automated biochemistry analyzer.Hematoxylin eosin(HE)staining was used to observe the pathological morphology of the thoracic aorta.ELISA was used to measure the contents of serum oxidized low-density lipoprotein(ox-LDL)and superoxide dismutase(SOD)activity.Western blot and real-time fluorescent quantitative PCR analysis were used to detect the expression levels of SIRT1 and FOXO3a protein and mRNA in the thoracic aorta.Results Compared with the control group,body weight at the 8th and 12th week,serum TC,TG,LDL-C,and ox-LDL contents of the model group mice were significantly increased(P<0.05,P<0.01),while the HDL-C contents,SOD activity,and the expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly decreased(P<0.05,P<0.01).HE staining showed thickening of the aortic intima,endothelial cell degeneration,swelling,and shedding.Compared with the model group,body weight at the 8th and 12th week,serum TC,TG,LDL-C,and ox-LDL contents of mice in the simvastatin group and moxibustion group were significantly decreased(P<0.01),while the serum SOD activity,expression levels of SIRT1 protein and mRNA in the thoracic aorta were significantly increased(P<0.01).The HDL-C contents were significantly increased in the simvastatin group(P<0.05).The thoracic aortic structure was more intact in both groups,with a more regular lumen and orderly arrangement of the elastic membrane in the media,and a slight amount of endothelial cell degeneration and swelling in the intima.There was no significant difference in the evaluated indexes between the moxibustion group and the simvastatin group and the pathological changes in the thoracic aorta were similar between the two groups.Conclusion Moxibustion can reduce the body weight of AS model mice,regulate lipid levels,repair vascular intima,and alleviate endothelial damage.Its mechanism of action may be related to the regulation of the SIRT1/FOXO3a signaling pathway to improve oxidative damage.

闫朝勃;伍先明;张宁;杨志虹;朱洲;喻华梅;贾晓琪;杨孝芳

湖南中医药大学针灸推拿与康复学院,长沙 410208贵州中医药大学针灸推拿学院,贵阳 550025湖南中医药大学针灸推拿与康复学院,长沙 410208||贵州中医药大学针灸推拿学院,贵阳 550025

动脉粥样硬化温和灸沉默信息调节因子1叉头框转录因子O3a

AtherosclerosisMild moxibustionSilent information regulator 1Forkhead box transcription factor O3a

《针刺研究》 2024 (004)

基于P2Y2受体调控SIRT1/FOXO3a信号通路研究艾灸抑制ApoE-/-小鼠动脉粥样硬化内皮细胞损伤机制

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国家自然科学基金项目(No.82160941、82360978);贵州省科技计划项目(No.黔科合基础-ZK[2022]一般499);贵州省卫生健康委科学技术基金项目(No.gzwkj2023-019);贵州省中医药管理局项目(No.QZYY-2021-021)

10.13702/j.1000-0607.20230578

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