Department of Intensive Care Unit, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Department of Intensive Care Unit, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China
Biosci Rep. 2018 May 8;38(3). doi: 10.1042/BSR20171629. Print 2018 Jun 29.
Glutamate receptors (N-methyl-d-aspartate receptor (NMDAR)) are expressed mainly in the central nervous system (CNS), but several potentially important exceptions are worth mentioning. Recently, NMDAR, a glutamate receptor, has been reported to be found in the lungs. NMDAR is activated in acute lung injury (ALI). Here, the present experiment was designed to examine whether NMDAR blockade (MK-801) ameliorates ALI through affecting neuropeptides in LPS-induced sepsis animal models. Male Kunming mice were divided into control group, LPS group, control + MK-801 group, and LPS + MK-801 group. Bronchoalveolar lavage fluid (BALF) was collected and evaluated. The lung histological pathology was assayed by immunocytochemistry staining. Western blot was used to measure PGP9.5, substance P (SP), and vasoactive intestinal polypeptide (VIP). Results showed that LPS-induced mice animal models were ameliorated by co-treatment with the MK-801, an uncompetitive NMDAR antagonist. Moreover, the protective effects of MK-801 attributed to the increased secretion of VIP and decreased secretion of SP. The results of the present study indicated that the blockade of NMDAR may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides.
谷氨酸受体（N-甲基-D-天冬氨酸受体（NMDAR））主要在中枢神经系统（CNS）中表达，但有几个潜在的重要例外值得一提。最近，据报道，谷氨酸受体 NMDAR 存在于肺部。NMDAR 在急性肺损伤（ALI）中被激活。在这里，本实验旨在研究 NMDAR 阻断（MK-801）是否通过影响 LPS 诱导的脓毒症动物模型中的神经肽来改善 ALI。雄性昆明小鼠分为对照组、LPS 组、对照组+MK-801 组和 LPS+MK-801 组。收集支气管肺泡灌洗液（BALF）并进行评估。通过免疫细胞化学染色测定肺组织病理学。Western blot 用于测量 PGP9.5、P 物质（SP）和血管活性肠肽（VIP）。结果表明，与 LPS 诱导的小鼠动物模型共处理可改善 MK-801，一种非竞争性 NMDAR 拮抗剂。此外，MK-801 的保护作用归因于 VIP 分泌增加和 SP 分泌减少。本研究的结果表明，通过调节神经肽，NMDAR 阻断可能代表治疗脓毒症相关 ALI 的一种有前途的治疗策略。
