We aim to investigate the role of A_2A receptor in peritonitis-related sepsis by injection of a fecal solution (FS) as a model of polymicrobial infection. C57/black J6 wild-type (WT) and A_2A-deficient mice (A_2AKO) were exposed to sepsis induced by intraperitoneal injection of a FS (FS-induced peritonitis) or instead was injected with saline buffer (Sham). Survival rate and sepsis score were measured up to 48 h. The presence of bacteria in tissue homogenates was analyzed. Telemetry and speckle laser Doppler were used for systemic blood pressure and peripheral blood perfusion analysis, respectively. Histological analysis and identification of active caspase 3 were performed in selected organs, including the liver. The survival rate of A_2AKO mice exposed to FS-induced peritonitis was significantly higher, and the sepsis score was lower than their respective WT counterpart. Injection of FS increases (50 to 150 folds) the number of colonies forming units in the liver, kidney, blood, and lung in WT mice, while these effects were significantly attenuated in A_2AKO mice exposed to FS-induced peritonitis. A significant reduction in both systolic and diastolic blood pressure, as well as in the peripheral perfusion was observed in WT and A_2AKO mice exposed to FS-induced peritonitis. Although, these last effects were significantly attenuated in A_2AKO mice. Histological analysis showed a large perivascular infiltration of polymorphonuclear in the liver of WT and A_2AKO mice exposed to FS-induced peritonitis, but again, this effect was attenuated in A_2AKO mice. Finally, high expression of active caspase 3 was found only in the liver of WT mice exposed to FS-induced peritonitis. The absence of the A_2A receptor increases the survival rate in mice exposed to polymicrobial sepsis. This outcome was associated with both hemodynamic compensation and enhanced anti-bacterial response.

我们旨在通过注射粪便溶液 (FS) 作为多微生物感染模型来研究 A _2A受体在腹膜炎相关败血症中的作用。C57/黑色 J6 野生型 (WT) 和 A _2A缺陷小鼠 (A _2A KO) 暴露于通过腹膜内注射 FS（FS 诱导的腹膜炎）诱导的败血症，或改为注射盐水缓冲液（假）。测量存活率和败血症评分长达 48 小时。分析了组织匀浆中细菌的存在。遥测和散斑激光多普勒分别用于全身血压和外周血灌注分析。在选定的器官（包括肝脏）中进行了活性 caspase 3 的组织学分析和鉴定。A的成活率暴露于 FS 诱导的腹膜炎的_2A KO 小鼠显着更高，并且败血症评分低于其各自的 WT 对应物。注射 FS 会增加（50 到 150 倍）WT 小鼠肝脏、肾脏、血液和肺中集落形成单位的数量，而这些影响在暴露于 FS 诱导的腹膜炎的A _2A KO 小鼠中显着减弱。在暴露于 FS 诱导的腹膜炎的WT 和 A _2A KO 小鼠中观察到收缩压和舒张压以及外周灌注显着降低。尽管如此，这些最后的影响在 A _2A KO 小鼠中显着减弱。组织学分析显示 WT 和 A _2A肝脏中大量血管周围多形核浸润KO 小鼠暴露于 FS 诱导的腹膜炎，但同样，这种影响在 A _2A KO 小鼠中减弱。最后，仅在暴露于 FS 诱导的腹膜炎的 WT 小鼠的肝脏中发现活性 caspase 3 的高表达。A _2A受体的缺失增加了暴露于多种微生物败血症的小鼠的存活率。这一结果与血流动力学补偿和增强的抗菌反应有关。