抑制NLRP3炎症小体中Caspase-1活化对大鼠颈动脉球囊损伤后内膜增生的保护作用  

Protective Effects of Inhibiting Caspase-1 Activation in NLRP3 Inflammasome against Intimal Hyperplasia after Balloon Injury of Carotid Artery in Rats

作　　者：刘颖[1] 刘艳秋[1] 李翠玲[1] 姚凤娟[1] 刘东红[1] 

机构地区：[1]中山大学附属第一医院超声科,广东广州510080

出　　处：《中山大学学报（医学科学版）》2017年第2期250-253,共4页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省省级产业技术研究与开发专项资金项目(20160904)

摘　　要：【目的】研究Caspase-1特异性抑制剂AC-YVAD-CMK对大鼠颈动脉球囊损伤后血管内膜增生的影响及可能机制。【方法】33只雄性成年SD大鼠,随机均分为假手术组、球囊损伤组、球囊损伤+AC-YVAD-CMK组。采用球囊损伤大鼠颈动脉的方法建立血管内膜增生动物模型,14天后留取球囊损伤段血管,15个血管片段制作冰冻切片,苏木精-伊红(HE)染色法测量内膜与中膜(I/M)面积比值;18根血管片段采用Western blot检测NOD样受体蛋白3(NLRP3)炎症小体、cleaved-Caspase-1、白介素(IL)-1β和IL-18的表达。【结果】HE染色发现,AC-YVAD-CMK显著抑制了内膜增生的程度(0.78±0.13 vs 1.52±0.14,P=0.000)。Western blot结果提示球囊损伤+AC-YVAD-CMK组中NLRP3蛋白表达较球囊损伤组显著降低(P=0.009);cleaved-Caspase-1蛋白在三组中的表达趋势与NLRP3蛋白表达一致(P=0.000)。且球囊损伤+AC-YVAD-CMK组大鼠的促炎性细胞因子IL-1β和IL-18水平较球囊损伤组显著降低(P=0.000)。【结论】AC-YVAD-CMK可以抑制大鼠颈动脉球囊损伤后内膜增生,其机制可能是其阻断Caspase-1蛋白活化,从而抑制促炎因子IL-1β和IL-18的释放而产生一定的保护作用。【Objective】To study the effects of Caspase-1 specific inhibitor AC-YVAD-CMK on intimal hyperplasia after carotidartery balloon injury in rats and its possible mechanism.【Methods】A total of 33 male adult SD rats were randomly divided into shamgroup,balloon injury group and balloon injury＋AC-YVAD-CMK group.Using the method of balloon injury to establish rat carotid ar-tery intimal hyperplasia animal model,rats were sacrificed and blood vessels were harvested 14 days after operation.Fifteen vascularsegments embedded in OCT and the intima to media（I/M）area ratio of neointima was measured by hematoxylin-eosin（HE）staining;18 vascular segments were harvested and the expression of NLRP3 inflammasome,cleaved-Caspase-1,interleukin（IL）-1β and IL-18 were measured by Western blot.【Results】HE staining showed that AC-YVAD-CMK significantly inhibited the degree of intimalhyperplasia compared with the balloon injury group[（0.78 ± 0.13）vs（1.52 ± 0.14）;P=0.000].The expression of NLRP3 inflamma-some was increased in balloon injury group while the AC-YVAD-CMK attenuates the expression of NLRP3（P=0.009）;The expres-sion of cleaved-Caspase-1 was in line with the expression of NLRP3（P=0.000）.The levels of pro-inflammatory cytokines IL-1βand IL-18 in balloon injury ＋ AC-YVAD-CMK group were significantly lower than those in the balloon injury group（P=0.000）.【Conclusion】AC-YVAD-CMK can attenuate intimal hyperplasia after balloon injury of carotid artery in rats,which might be relatedto its effect on inhibiting the activation of Caspase-1,which could affect the release of pro-inflammatory cytokine of IL-1β and IL-18.

关 键 词：球囊损伤 内膜增生 大鼠 NLRP3炎症小体 AC-YVAD-CMK 

分 类 号：R543.3[医药卫生—心血管疾病]