Liu Lingling, Wang Shuzhi, Jiang Lianhao, Wang Jiwei, Chen Jun, Zhang Hongtao, Wang Yuanlin
Department of Anesthesiology, Tianjin Huanhu Hospital, NO. 6 Jizhao Road, Jinnan District, Tianjin, 300350, China.
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenrative Diseases, Tianjin, 300350, China.
BMC Chem. 2025 May 22;19(1):138. doi: 10.1186/s13065-025-01513-2.
Hydrogen gas has demonstrated significant antioxidant and anti-inflammatory properties, suggesting potential therapeutic benefits in TBI.
We subjected to controlled cortical impact in mice to construct TBI model. They received an intraperitoneal injection of MCC950, a selective NLRP3 inhibitor, at 10 mg/kg 30 min before TBI. Inhalation of 2% H is adopted in TBI mice for 60 min, starting 1 and 6 h post-TBI. 24 h after H inhalation, we extracted tissues and analyzed injury related changes. The H levels in arterial and venous were tracked after inhalation. Lung tissue was examined for histopathological changes and apoptosis using H&E and TUNEL assays. The total protein in the BALF, oxygenation index, lung wet-to-dry weight ratio, and lung MPO activity were measured to evaluate the severity of TBI-induced lung injury. Protein and mRNA levels of NLRP3, ASC, Caspase-1, IL-18, and IL-1β in the lung tissue were quantified using western blotting and quantitative PCR. The expression changes and distribution status of NLRP3 and Caspase-1 were examined by immunofluorescence and immunohistochemistry staining.
Significant lung injury at 24 h post-TBI got significantly reduced by treatment of 2% H. TBI activated the NLRP3 inflammasome, increasing NLRP3, ASC, and caspase-1 levels, to lead to higher IL-1β and IL-18 secretion in the lungs. Blocking NLRP3 reduced lung damage from TBI, and its combination with 2% H provided better protection than either treatment alone.
2% H can protect against TBI-induced lung injury by inhibiting NLRP3 inflammasome activation, thereby alleviating inflammation and inhibiting apoptosis.
氢气已显示出显著的抗氧化和抗炎特性，提示其在创伤性脑损伤（TBI）中可能具有治疗益处。
我们对小鼠进行控制性皮质撞击以构建TBI模型。在TBI前30分钟，给它们腹腔注射10mg/kg的选择性NLRP3抑制剂MCC950。在TBI小鼠中，于TBI后1小时和6小时开始吸入2%氢气，持续60分钟。氢气吸入24小时后，提取组织并分析与损伤相关的变化。吸入后追踪动脉和静脉中的氢气水平。使用苏木精-伊红（H&E）染色和TUNEL检测法检查肺组织的组织病理学变化和细胞凋亡情况。测量支气管肺泡灌洗液（BALF）中的总蛋白、氧合指数、肺湿重与干重之比以及肺髓过氧化物酶（MPO）活性，以评估TBI诱导的肺损伤严重程度。使用蛋白质免疫印迹法和定量聚合酶链反应（PCR）对肺组织中NLRP3、凋亡相关斑点样蛋白（ASC）、半胱天冬酶-1（Caspase-1）、白细胞介素-18（IL-18）和白细胞介素-1β（IL-1β）的蛋白质和mRNA水平进行定量分析。通过免疫荧光和免疫组织化学染色检查NLRP3和Caspase-1的表达变化和分布状态。
TBI后24小时时的显著肺损伤通过2%氢气治疗得到显著减轻。TBI激活了NLRP3炎性小体，增加了NLRP3、ASC和Caspase-1水平，导致肺中IL-1β和IL-18分泌增加。阻断NLRP3可减轻TBI引起的肺损伤，并且其与2%氢气联合使用比单独使用任何一种治疗方法提供了更好的保护。
2%氢气可通过抑制NLRP3炎性小体激活来保护免受TBI诱导的肺损伤，从而减轻炎症并抑制细胞凋亡。
