Cognitive dysfunction caused by sepsis-associated encephalopathy (SAE) is still poorly understood. It is reported that vasoactive intestinal peptide (VIP) exerts its anti-inflammatory effects in multiple diseases, while its biological function in SAE remains unclear. We aimed to figure out whether VIP has influence on sepsis-induced neuroinflammation and cognitive dysfunction. To induce sepsis, rats were subjected to cecal ligation and puncture (CLP) operation. Morris water maze test and fear conditioning test were conducted to reveal cognitive dysfunctions. TUNEL assay was performed to evaluate apoptosis. We found out that the expression of VIP was downregulated in the hippocampus of septic rats. VIP was verified to attenuate sepsis-induced memory impairment following CLP. Additionally, we examined apoptosis and inflammation in rats’ hippocampus. It is worth noting that VIP inhibited the apoptosis in the hippocampus and reduced the productions of proinflammatory cytokines TNF-α, IL-6 and IL-1β. Furthermore, our data confirmed that VIP was involved in regulating the TLR-4/NF-κB signaling. In conclusion, VIP inhibited neuroinflammation and cognitive impairment in hippocampus of septic rats through the TLR-4/NF-κB signaling pathway.

由脓毒症相关脑病 (SAE) 引起的认知功能障碍仍然知之甚少。据报道，血管活性肠肽（VIP）在多种疾病中发挥抗炎作用，而其在SAE中的生物学功能尚不清楚。我们旨在弄清楚 VIP 是否对脓毒症引起的神经炎症和认知功能障碍有影响。为了诱导脓毒症，对大鼠进行盲肠结扎和穿刺（CLP）手术。进行莫里斯水迷宫测试和恐惧条件测试以揭示认知功能障碍。进行 TUNEL 测定以评估细胞凋亡。我们发现脓毒症大鼠海马中VIP的表达下调。VIP 经证实可减轻 CLP 后脓毒症引起的记忆障碍。此外，我们检查了大鼠海马的细胞凋亡和炎症。值得注意的是，VIP抑制海马细胞凋亡，减少促炎细胞因子TNF-α、IL-6和IL-1β的产生。此外，我们的数据证实 VIP 参与调节 TLR-4/NF-κB 信号传导。总之，VIP通过TLR-4/NF-κB信号通路抑制脓毒症大鼠海马神经炎症和认知障碍。