Zhou Shuang, Li Yuhua, Hong Yi, Zhong Zhitao, Zhao Min
Department of Emergency, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, 110004, China.
Department of Critical Care Medicine, Wuhan Children's Hospital, Wuhan, Hubei Province, 430014, China.
Eur J Pharmacol. 2023 Apr 15;945:175616. doi: 10.1016/j.ejphar.2023.175616. Epub 2023 Feb 28.
Puerarin (Pue), an isoflavone compound extracted from Pueraria, has been shown to inhibit inflammation and reduce cerebral edema. The neuroprotective effect of puerarin has attracted much attention in recent years. Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis that causes damage to the nervous system. This study aimed to investigate the effect of puerarin on SAE and elucidate the potential underlying mechanisms. A rat model of SAE was established by cecal ligation and puncture, and puerarin was injected intraperitoneally immediately after the operation. Puerarin was found to improve the survival rate and neurobehavioral score of SAE rats, alleviate symptoms, inhibit the level of brain injury markers NSE and S100β, and improve the pathological changes in rat brain tissue. Puerarin was also found to inhibit the level of factors related to the classical pathway of pyroptosis, such as NLRP3, Caspase-1, GSDMD, ASC, IL-1β, and IL-18. Puerarin also reduced the brain water content and penetration of Evan's Blue dye in SAE rats, and reduced the expression of MMP-9. In the in vitro experiments, we further confirmed the inhibitory effect of puerarin on neuronal pyroptosis by establishing a pyroptosis model in HT22 cells. Our findings suggest that puerarin may improve SAE by inhibiting the classical pathway of NLRP3/Caspase-1/GSDMD-mediated pyroptosis and reducing blood-brain barrier damage, thus playing a role in brain protection. Our study may provide a novel therapeutic strategy for SAE.
葛根素（Pue）是从葛根中提取的一种异黄酮化合物，已被证明具有抗炎和减轻脑水肿的作用。近年来，葛根素的神经保护作用备受关注。脓毒症相关性脑病（SAE）是脓毒症的一种严重并发症，会对神经系统造成损害。本研究旨在探讨葛根素对SAE的影响，并阐明其潜在的作用机制。通过盲肠结扎和穿刺建立SAE大鼠模型，并在术后立即腹腔注射葛根素。结果发现，葛根素可提高SAE大鼠的存活率和神经行为评分，缓解症状，抑制脑损伤标志物NSE和S100β的水平，并改善大鼠脑组织的病理变化。还发现葛根素可抑制与焦亡经典途径相关的因子水平，如NLRP3、Caspase-1、GSDMD、ASC、IL-1β和IL-18。葛根素还降低了SAE大鼠的脑含水量和伊文思蓝染料的渗透，并降低了MMP-9的表达。在体外实验中，我们通过在HT22细胞中建立焦亡模型进一步证实了葛根素对神经元焦亡的抑制作用。我们的研究结果表明，葛根素可能通过抑制NLRP3/Caspase-1/GSDMD介导的焦亡经典途径和减轻血脑屏障损伤来改善SAE，从而发挥脑保护作用。我们的研究可能为SAE提供一种新的治疗策略。
