Abstract: Objective To explore whether heat stress would increase pulmonary capillary permeability via activating the NLRP3 (NLR family, pyrin domain-containing 3) inflammasome. Methods C57BL / 6 mice and pulmonary microvascular endothelial cells (PMVECs) were underwent 42 ℃ heat stress. The mice were randomly divided into two groups: control group and heat stress group, 12 mice for each group. The PMVECs were randomly divided into five groups:control group, heat stress group, heat stress + TEMPO group, heat stress + Z-VAD-FMK group and heat stress + interleukin-1 receptor antagonist (IL-1Ra) group, 4 cases for each group. Caspase-1, IL-1β and tight junction proteins (ZO-1, occludin,claudin-5) expressions were assessed by Western blot assay or double immunofluorescence. The permeability of blood-brain barrier was assessed by Evans blue staining. Results The concentrations of Evans blue in lung tissue were significantly increased in heat stress group compared with those of control group (P＜0.01). The expression levels of ROS, caspase-1 and IL-1β were significantly increased, and the expression levels of ZO-1, occludin and claudin-5 were significantly decreased,in heat stress group compared with those of control group (P＜0.01). Scavenging of ROS decreased the expression levels of caspase-1 (P＜0.01). The pharmacological (Z-VAD-FMK) inhibition of NLRP3 inflammasome activation decreased the expression levels of IL-1β (P＜0.01). The pharmacological (IL-1Ra) blocking of IL-1β receptor increased the expression levels of tight junction protein (ZO-1: P＜0.01, occludin: P＜0.01, claudin-5: P＜0.01). Conclusion Heat stress may increase pulmonary capillary permeability via the activation of NLRP3 inflammasome and the reducing of tight junction protein expression.

Key words: heat stroke, inflammasomes, interleukin-1beta, tight junction proteins, NLR family, pyrin domaincontaining 3 protein, capillary permeability, heat stress