Protective Effects of Inhibiting Caspase-1 Activation in NLRP3 Inflammasome against Intimal Hyperplasia after Balloon Injury of Carotid Artery in Rats / 中山大学学报(医学科学版)

ABSTRACT

[Objective]To study the effects of Caspase-1 specific inhibitor AC-YVAD-CMK on intimal hyperplasia after carotid artery balloon injury in rats and its possible mechanism.[Methods]A total of 33 male adult SD rats were randomly divided into sham group,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 vascular segments 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)-1βand IL-18 were measured by Western blot.[Results]HE staining showed that AC-YVAD-CMK significantly inhibited the degree of intimal hyperplasia 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 related to its effect on inhibiting the activation of Caspase-1,which could affect the release of pro-inflammatory cytokine of IL-1βand IL-18.