摘要
目的探讨白藜芦醇(Rev)对动脉粥样硬化(AS)的保护作用,阐明Rev对lncRNA MALAT1调控及MALAT1在AS中的表达与作用。方法 ApoE^(-/-)小鼠随机分成2组:高脂饮食(HFD)处理组;HFD同时给予Rev组,16周建立AS模型。采用HE染色检测小鼠主动脉斑块面积;电镜检测泡沫细胞的形成;采用实时定量PCR检测动脉斑块中MALAT1表达水平,以及Rev对MALAT1的影响。体外实验,检测Rev对MALAT1、IL-6、IL-1β、TNF-α的影响;MALAT1对炎症因子IL-6、IL-1β、TNF-α的影响;游离胆固醇(FC)对MALAT1表达的影响。结果 Rev处理组明显缩小动脉斑块,并减少泡沫细胞的形成。MALAT1在动脉斑块中表达量降低,并且Rev可以明显逆转MALAT1的表达。此外, Rev可剂量依赖性降低IL-6、IL-1β、TNF-α表达。敲减MALAT1能促进炎症因子IL-6和TNF-α的表达。FC可使MALAT1的表达降低。结论 Rev可能通过调控MALAT1,进而调控炎症因子IL-6、IL-1β、TNF-α的表达,发挥抗AS作用。
Aim To investigate the protective effect of resveratrol(Rev)on atherosclerosis(AS),and clarify the roleof Rev in regulating lncRNA MALAT1(MALAT1)and the role of MALAT1in AS.Methods ApoE^-/-mice were randomly divided into two groups:the high-fat diet(HFD)group,the HFD plus Rev treatment group,and the atherosclerosis model was established for16weeks.Hematoxylin-eosin(HE)staining was used to detect the area of aortic plaques in mice.And electron microscopy was performed to measure the formation of foam cells.The effects of Rev on MALAT1,inflammatory cytokine(IL-6,IL-1βand TNF-α)were examined using real time PCR.In addition,the roles of MALAT1on inflammatory cytokine,and the influence of free cholesterol(FC)on the expression of MALAT1were measured by real time PCR.Results The Rev treatment group significantly reduced arterial plaque areas and foam cell formation.In normal peritoneal macrophages,Rev could increase the expression of MALAT1,and FC could down-regulate MALAT1.Furthermore,Rev could decrease the expression of IL-6,IL-1βand TNF-αin a dose-dependent manner.Knockdown of MALAT1promoted the mRNA expression of IL-6and TNF-α.Conclusions Rev may modulate the expression of inflammatory cytokine IL-6,IL-1βand TNF-αby affecting the level of MALAT,thereby exerting the anti-atherogenic effects.
作者
贾雪凌
范玉华
潘昱
方坤
赵宝山
王麟
陈红阳
蒋雅楠
宋印利
JIA Xue-ling;FAN Yu-hua;PAN Yu;FANG Kun;ZHAO Bao-shan;WANG Lin;CHEN Hong-yang;JIANG Ya-nan;SONG Yin-li(Dept of Pathology and Pathophysiology,Basic Medical School College of Pharmacy,Harbin Medical University, Daqing,Heilongjiang 163319,China;Biotechnological Pharmaceutics Faculty, College of Pharmacy,Harbin Medical University, Daqing,Heilongjiang 163319,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2019年第1期35-40,共6页
Chinese Pharmacological Bulletin
基金
黑龙江省自然科学基金资助项目(No QC2016112)
国家自然科学基金资助项目(No 81503069)
