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

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。

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

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.