MM. Department of Neurosurgery - 904th Hospital of Joint Logistic Support Force of PLA - Wuxi Clinical College of Anhui Medical University - Wuxi, China.
BS. Department of Neurosurgery - 904th Hospital of Joint Logistic Support Force of PLA - Wuxi Clinical College of Anhui Medical University - Wuxi, China.
Acta Cir Bras. 2022 Apr 20;37(1):e370108. doi: 10.1590/acb370108. eCollection 2022.
Traumatic brain injury (TBI) remains a major public health problem and cause of death. Ulinastatin (UTI), a serine protease inhibitor, has been reported to have an anti-inflammatory effect and play a role in immunoregulation and organ protection by reducing reactive oxygen species (ROS) production, oxidative stress and inflammation. However, the neuroprotective of UTI in TBI has not been confirmed. Therefore, this study aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in TBI-induced EBI in a C57BL/6 mouse model.
The neurological score and brain water content were evaluated. Enzyme-linked immunosorbent assay was used to detect neuroinflammatory cytokine levels, ROS and malondialdehyde detection to evaluate oxidative stress levels, and TUNEL staining and western blotting to examine neuronal damages and their related mechanisms.
Treatment with UTI markedly increased the neurological score; alleviated brain oedema; decreased the inflammatory cytokine tumour necrosis factor a, interleukin-1β (IL-1β), IL-6 and nuclear factor kappa B (NF-kB) levels; inhibited oxidative stress; decreased caspase-3 and Bax protein expressions; and increased the Bcl-2 levels, indicating that UTI-mediated inhibition of neuroinflammation, oxidative stress and apoptosis ameliorated neuronal death after TBI. The neuroprotective capacity of UTI is partly dependent on the TLR4/NF-kB/p65 signalling pathway.
Therefore, this study reveals that UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation, oxidative stress and apoptosis.
颅脑损伤（TBI）仍然是一个主要的公共卫生问题和死亡原因。尿胰蛋白酶抑制剂（UTI）是一种丝氨酸蛋白酶抑制剂，据报道具有抗炎作用，并通过减少活性氧（ROS）的产生、氧化应激和炎症来发挥免疫调节和器官保护作用。然而，UTI 在 TBI 中的神经保护作用尚未得到证实。因此，本研究旨在探讨 UTI 在 C57BL/6 小鼠 TBI 诱导的 EBI 中的神经保护作用及其潜在的分子机制。
评估神经功能评分和脑水含量。采用酶联免疫吸附试验检测神经炎症细胞因子水平，ROS 和丙二醛检测评估氧化应激水平，TUNEL 染色和 Western blot 检测神经元损伤及其相关机制。
UTI 治疗显著提高了神经功能评分；减轻脑水肿；降低炎症细胞因子肿瘤坏死因子-α、白细胞介素-1β（IL-1β）、白细胞介素-6 和核因子 kappa B（NF-kB）水平；抑制氧化应激；降低半胱天冬酶-3 和 Bax 蛋白表达；并增加 Bcl-2 水平，表明 UTI 介导的抑制神经炎症、氧化应激和细胞凋亡改善了 TBI 后的神经元死亡。UTI 的神经保护能力部分依赖于 TLR4/NF-kB/p65 信号通路。
因此，本研究表明 UTI 通过保护神经免受神经炎症、氧化应激和细胞凋亡，改善了小鼠的神经功能预后并减少了神经元死亡。
