α-硫辛酸通过抑制NF-κB信号通路干预兔动脉粥样硬化

α-lipoic acid interferes with atherosclerosis in rabbits by inhibiting NF-κB signaling pathway

为探讨α-硫辛酸(alpha-lipoic acid,ALA)干预对兔动脉粥样硬化(atherosclerosis,AS)的作用及可能机制,将40只新西兰大白兔随机均分为4组:正常组、正常+ALA组、模型组及模型+ALA组。其中,模型组和模型+ALA组实验兔通过联合液氮损伤和高脂饲养构建兔AS模型,正常+ALA组和模型+ALA组实验兔给予连续14 d静脉注射ALA(50 mg/kg)。采用H-E染色观察兔动脉组织病变;Western blotting检测动脉组织NF-κB信号通路蛋白的表达水平;qRT-PCR检测细胞黏附分子(cell adhesion molecule,CAM)和趋化因子的mRNA表达水平;ELISA检测各组血清炎性因子的表达水平。结果显示,模型组动脉管壁增厚,镜下可见脂质沉积和炎症细胞浸润,提示造模成功。模型组动脉组织NF-κB磷酸化水平、黏附分子等mRNA表达水平和血清炎性因子表达水平均增加,与正常组相比差异均具有统计学意义(均P<0.05)。ALA治疗后,动脉组织的病理情况明显改善,NF-κB磷酸化水平和黏附分子等mRNA表达水平显著降低,炎性因子表达水平也显著下降(均P<0.05)。由此,ALA可能通过抑制NF-κB信号通路降低机体的炎症反应水平,进而干预兔AS进程。

This study explored the efficacy and possible mechanism of alpha-lipoic acid(ALA)intervention on the rabbit atherosclerosis(AS)model.Forty New Zealand white rabbits were randomly divided into four groups:normal group,normal+ALA treatment group,ASmodel group and AS model+ALA treatment group.The rabbit AS model was established by combined treatment of liquid nitrogen-induced injury and high-fat diet.Animals in the normal+ALA treatment group and AS model+ALA treatment group were given ALA(50 mg/kg)by continuously intravenous injection for fourteen days.Subsequently,the pathological morphology of arterial tissues was evaluated by H-E staining.Next,the protein levels of NF-κB signaling pathway were detected by Western blotting;The mRNA levels of cell adhesion molecule(CAM)and chemokines were detected by qRT-PCR and the serum levels of inflammatory cytokines were measured by ELISA.The results showed microscopically significantly narrowed arterial lumen with obvious lipid deposition and inflammatory cell infiltration in the AS model group,indicating that the model was successfully established.Our results indicated that the phosphorylation levels of NF-κB signaling pathway proteins,mRNA levels of CAM and the serum levels of inflammatory cytokines were all increased significantly(all P<0.05)in the AS model group.Intriguingly,after the treatment with ALA,compared with those in the model group,the pathological manifestations of arterial tissues were significantly improved.In agreement with the pathological results,the phosphorylation of NF-κB,the mRNA levels of CAM and the serum inflammatory cytokines levels all decreased(all P<0.05)upon ALA treatment.In conclusion,ALA decreases the inflammatory response by suppressing NF-κB signaling pathway,thus suppresses the AS pathogenesis in the rabbit model.