Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction closely associated with mortality in the acute phase of sepsis. Abnormal neurotransmitters release, such as glutamate, plays a crucial role in the pathological mechanism of SAE. Munc18-1 is a key protein regulating neurotransmission. However, whether Munc18-1 plays a role in SAE by regulating glutamate transmission is still unclear. In this study, a septic rat model was established by the cecal ligation and perforation. We found an increase in the content of glutamate in the hippocampus of septic rat, the number of synaptic vesicles in the synaptic active area and the expression of the glutamate receptor NMDAR1. Meanwhile, it was found that the expressions of Munc18-1, Syntaxin1A and Synaptophysin increased, which are involved in neurotransmission. The expression levels of Syntaxin1A and Synaptophysin in hippocampus of septic rats decreased after interference using Munc18-1siRNA. We observed a decrease in the content of glutamate in the hippocampus of septic rats, the number of synaptic vesicles in the synaptic activity area and the expression of NMDAR1. Interestingly, it was also found that the down-regulation of Munc18-1 improved the vital signs of septic rats. This study shows that CLP induced the increased levels of glutamate in rat hippocampus, and Munc18-1 may participate in the process of hippocampal injury in septic rats by affecting the levels of glutamate via regulating Syntaxin1A and Synaptophysin. Munc18-1 may serve as a potential target for SAE therapy.

脓毒症相关脑病 (SAE) 是一种弥漫性脑功能障碍，与脓毒症急性期死亡率密切相关。异常的神经递质释放，如谷氨酸，在SAE的病理机制中起着至关重要的作用。Munc18-1 是调节神经传递的关键蛋白。然而，Munc18-1 是否通过调节谷氨酸传递在 SAE 中起作用仍不清楚。本研究采用盲肠结扎穿孔法建立脓毒症大鼠模型。我们发现脓毒症大鼠海马中谷氨酸含量增加，突触活动区突触小泡数量增加，谷氨酸受体NMDAR1表达增加。同时，发现参与神经传递的Munc18-1、Syntaxin1A和Synaptophysin的表达增加。Munc18-1siRNA干扰后，脓毒症大鼠海马Syntaxin1A和Synaptophysin的表达水平降低。我们观察到败血症大鼠海马区谷氨酸含量下降，突触活动区突触小泡数量下降，NMDAR1表达下降。有趣的是，还发现Munc18-1的下调改善了败血症大鼠的生命体征。本研究表明CLP诱导大鼠海马谷氨酸水平升高，Munc18-1可能通过调节Syntaxin1A和Synaptophysin影响谷氨酸水平参与脓毒症大鼠海马损伤过程。Munc18-1 可作为 SAE 治疗的潜在靶标。我们观察到败血症大鼠海马区谷氨酸含量下降，突触活动区突触小泡数量下降，NMDAR1表达下降。有趣的是，还发现Munc18-1的下调改善了败血症大鼠的生命体征。本研究表明CLP诱导大鼠海马谷氨酸水平升高，Munc18-1可能通过调节Syntaxin1A和Synaptophysin影响谷氨酸水平参与脓毒症大鼠海马损伤过程。Munc18-1 可作为 SAE 治疗的潜在靶标。我们观察到败血症大鼠海马区谷氨酸含量下降，突触活动区突触小泡数量下降，NMDAR1表达下降。有趣的是，还发现Munc18-1的下调改善了败血症大鼠的生命体征。本研究表明CLP诱导大鼠海马谷氨酸水平升高，Munc18-1可能通过调节Syntaxin1A和Synaptophysin影响谷氨酸水平参与脓毒症大鼠海马损伤过程。Munc18-1 可作为 SAE 治疗的潜在靶标。还发现Munc18-1的下调改善了败血症大鼠的生命体征。本研究表明CLP诱导大鼠海马谷氨酸水平升高，Munc18-1可能通过调节Syntaxin1A和Synaptophysin影响谷氨酸水平参与脓毒症大鼠海马损伤过程。Munc18-1 可作为 SAE 治疗的潜在靶点。还发现Munc18-1的下调改善了败血症大鼠的生命体征。本研究表明CLP诱导大鼠海马谷氨酸水平升高，Munc18-1可能通过调节Syntaxin1A和Synaptophysin影响谷氨酸水平参与脓毒症大鼠海马损伤过程。Munc18-1 可作为 SAE 治疗的潜在靶点。