激活瞬时受体电位香草醛亚家族1改善平滑肌源性泡沫细胞形成机制研究  

Activation of TRPV1improves foam cell formation of vascular smooth muscle cells during atherosclerosis

作　　者：尹延伟 石进 孙倩倩 陈大伟 赵发国 杨芬 宋琛 李文平 李金花 Yin Yanwei;Shi Jin;Sun Qianqian;Chen Dawei;Zhao Faguo;Yang Fen;Song Chen;Li Wenping;Li Jinhua(Department of Neurology,Air Force Medical Center,Beijing 100142,China)

机构地区：[1]空军特色医学中心神经内科,北京100142 [2]北京卫戍区第九离职干部休养所

出　　处：《中华老年心脑血管病杂志》2020年第1期66-69,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：北京市科技新星计划（Z171100001117094）;国家自然科学基金（81500356）

摘　　要：目的探讨瞬时受体电位香草醛亚家族1(TRPV1)在血管平滑肌细胞(VSMC)泡沫化过程中的作用及可能的机制。方法将野生型C57BL/6J雄性小鼠来源主动脉VSMC不加任何试剂刺激作为对照组,另将野生型C57BL/6J雄性小鼠和Toll样受体(TLR4)基因敲除(TLR4-/-)雄性小鼠来源主动脉VSMC使用氧化型低密度脂蛋白(oxLDL)80μg/ml刺激72h,建立oxLDL细胞模型,依次作为oxLDL组、辣椒素组(造模前预先用辣椒素50μmol/ml刺激VSMC 12h)和TLR4-/-组,每组5例。采用油红O染色观察VSMC内脂质聚积情况;检测VSMC内胆固醇、TRPV1、TLR4蛋白及炎性因子白细胞介素6(IL-6)和TNF-α表达。结果与对照组比较,oxLDL组VSMC泡沫化程度、胆固醇水平明显升高,TLR4及其介导的IL-6[(44.03±3.76)ng/L vs (25.64±4.84)ng/L]、TNF-α表达[(155.64±13.32)ng/L vs (89.86±9.18)ng/L]明显升高,差异有统计学意义(P<0.05),而TLR4-/-组和辣椒素组VSMC泡沫化程度、胆固醇水平、TLR4及其介导的IL-6、TNF-α表达与对照组比较,差异无统计学意义(P>0.05);与oxLDL组比较,辣椒素组VSMC中TRPV1蛋白表达明显上调,同时伴随VSMC泡沫化程度、胆固醇水平、TLR4及其介导的IL-6、TNF-α表达明显下调,差异有统计学意义(P<0.05)。结论激活TRPV1可通过干扰TLR4介导的炎性反应抑制VSMC泡沫化。Objective To study the role of TRPV1 in foam cell formation of VSMC and its mechanism.Methods Primary VSMC isolated from the thoracic aorta of wild male(C57 BL/6 J)mice not stimulated with any agent served as a control group and TLR4-/-mice were divided into oxLDL group,TLR4-/-group and capsaicin group(5 in each group).The intracellular lipid deposition was identified with oil Red O staining.The serum cholesterol level was measured and the expressions of TRPV1,TLR4 protein,IL-6 and TNF-αin VSMC were detected.Results The foam cell formation rate,serum cholesterol level and TLR4,IL-6,TNF-αexpression levels in VSMC were significantly higher in oxLDL group than in control group(P<0.05)with no significant difference detected in TLR4-/-group,capsaicin group and control group(P>0.05).The TRPV1 and capsaicin expression levels were significantly higher while the foam cell formation rate,serum cholesterol level and TLR4,IL-6,TNF-αexpression levels in VSMC were significantly lower in capsaicin group than in oxLDL group(P<0.05).Conclusion Activation of TRPV1 can inhibit foam cell formation of VSMC by supressing TLR4-mediated inflammatory reactions.

关 键 词：瞬时受体电位通道 肌 平滑 血管 泡沫细胞 

分 类 号：R543.5[医药卫生—心血管疾病]