阿托伐他汀抑制动脉粥样硬化患者NLRP3炎性体途径的研究

Atorvastatin inhibits NLRP3 inflammasome pathway in patients with atherosclerosis

目的研究治疗动脉粥样硬化(AS)药物阿托伐他汀对含热蛋白结构域3的核苷酸结合寡聚化样受体(NLRP3)炎性体的调节作用。方法采用ELISA法测定30例AS患者经阿托伐他汀治疗前后IL-1β和IL-18在血浆和单核细胞来源巨噬细胞(MDM)中的表达水平;采用实时荧光定量PCR法检测炎性体相关分子如NLRP3、凋亡相关的点状蛋白(ASC)、IL-1βm RNA的表达水平;在体外用不同浓度和时间的阿托伐他汀处理单核巨噬细胞株(THP-1),观察其对尼日利亚菌素激活NLRP3炎性体的调节作用。结果 AS患者经阿托伐他汀治疗后血浆和MDM中的IL-1β和IL-18的表达水平均低于治疗前,差异均有统计学意义(均P<0.05);MDM中NLPR3、ASC和IL-1βm RNA表达均低于治疗前,差异均有统计学意义(均P<0.05);与对照组比较,低、中、高浓度组的阿托伐他汀以及用阿托伐他汀处理12、24、48h后IL-1β和IL-18的表达水平均下降,差异均有统计学意义(均P<0.05),且随着阿托伐他汀浓度越大、处理时间越长,下降越明显(均P<0.01)。结论阿托伐他汀可能通过抑制AS患者NLRP3炎性体活化发挥其治疗作用。

Objective To investigate the effect of atorvastatin on NLRP3 inflammasome pathway in patients with atherosclerosis.Methods Thirty patients with atherosclerosis treated with atorvastatin were enrolled in the study. The IL-1, IL-18 levels in plasma and monocytes derived macrophages(MDMs) were measured by ELISA;the expression of NLRP3, ASC and IL-1 β m RNA in MDMs were detected by real time RT-PCR before and 2 months after atorvastatin treatment. Human monocyte THP-1 cells were treated with atorvastatin at different concentrations and for different time, its effect on NLRP3 after stimulation by nigericin was investigated. Results Plasma IL-1βand IL-18 levels in atherosclerosis patients was significantly decreased after atorvastatin treatment(all P<0.05). Expression of NLRP3, ASC and IL-1β m RNA in MDMs and IL-1β, IL-18 secreted by MDMs also decreased significantly(all P<0.05). Atorvastatin inhibited the secretion of IL-1β and IL-18 in THP-1 cells stimulated with nigericin(all P<0.05). Conclusion Atorvastatin may exert its therapeutic effect by inhibiting NLRP3 inflammasome pathway.