To explore the roles of mesenteric lymph on lung injury in heatstroke (HS), HS rat model was prepared in a prewarmed incubator. Vascular endothelium injury biomarkers (circulating endothelial cell [CEC] as well as von Willebrand factor [vWF] and thrombomodulin [TM]), proinflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], IL-6, and high mobility group box 1), and coagulant markers (activated partial thromboplastin time, prothrombin time, D-Dimer, and platelet count) were tested in HS and HS with mesenteric lymph duct ligation (LDL) rats. In addition, lung histopathology; arterial blood gas; Evans Blue dye (EBD) and protein lung permeability; intralung inflammatory parameters including bronchoalveolar lavage fluid (BALF) TNF-α, IL-1β, and IL-6 levels; myeloperoxidase (MPO) activity; and vWF immune staining were analyzed. LDL prolonged HS onset time but not HS survival time. LDL significantly attenuated endothelial cell injury for decreased CEC counts as well as plasma vWF and TM concentrations; downregulated systemic inflammation for decreased plasma TNF-α, IL-1β, IL-6, and high mobility group box 1 levels; and ameliorated coagulant disorders for decreased activated partial thromboplastin time, prothrombin time, and D-Dimer levels as well as increased platelet counts. LDL also significantly reduced acute lung pathological injury; improved lung function indexes including arterial blood PaO2, pH, PaCO2, and lactic acid; decreased BALF TNF-α, IL-1β, and IL-6 levels and lung MPO activity; improved EBD and protein lung permeability; and inhibited lung vascular endothelium vWF expression. However, all of these parameters were not recovered to the normal states. In summary, LDL developed protection roles systemically and alleviated lung injury in HS rats which indicated that modulating mesenteric lymph flow may have some potential benefits in HS.

Background: Previous studies have suggested that NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays an important role in heat stroke (HS). As a common complication in HS, thrombocytopenia has been widely considered as a good predictor of HS-related mortality. However, little is known about the relationship between inflammasome and thrombocytopenia as well as platelet activation in HS. Methods: We established a rat HS model to investigate the roles of NLRP3 inflammasome in both platelet activation and thrombocytopenia, platelet activation was reflected with Flow cytometry while thrombocytopenia was measured by platelet count. The colocalization of NLRP3 inflammasome was detected by confocal fluorescence microscopy. Mitochondrial-derived reactive oxygen species (ROS) were detected using the molecular probes. Plasma HMGB1 levels were measured by ELISA.Results: Activation of the inflammasome was detected in platelet of rats in HS. Elevated ROS activated NLRP3 inflammasome in HS group could significantly induce platelet activation and thrombocytopenia. The upregulated P-selectin (CD62P ) and decreased platelet count triggered by NLRP3 inflammasome were attributed to the high mobility group box protein 1 (HMGB1) in plasma. Moreover, inhibition of HMGB1, caspase-1, NLRP3, or ROS in rats with HS suppressed platelet activation and the decline of platelet count. Similar results were obtained when the receptor toll-like receptor 4 (TLR4) / advanced glycation end product (RAGE) was blocked. Conclusions: This study indicated that platelets were activated by NLRP3 inflammasome through TLR4/RAGE/HMGB1 signaling pathway. The NLRP3 inflammasome might be the potential target for HS treatment.