分子氢减轻创伤性脑损伤后的肺损伤：细胞焦亡和细胞凋亡。

Molecular hydrogen alleviates lung injury after traumatic brain injury: Pyroptosis and apoptosis.

机构信息

Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, 246 XueFu Road, NanGang District, Harbin, 150086, China.

Department of Anesthesiology, People's Hospital of Hegang City, Heilongjiang, 154101, China.

出版信息

Eur J Pharmacol. 2022 Jan 5;914:174664. doi: 10.1016/j.ejphar.2021.174664. Epub 2021 Dec 6.

DOI:10.1016/j.ejphar.2021.174664

PMID:34883075

Abstract

BACKGROUND

Traumatic brain injury (TBI)-induced acute lung injury (ALI) is a critical condition, and inflammation and apoptosis play essential roles. Molecular hydrogen (H) exerts anti-inflammatory and anti-apoptotic effects. Our previous work has shown that 42% H can improve TBI. In the current study, we tested the hypothesis that inhalation of hydrogen (42% H, 21% O, balanced nitrogen) for 1 h per day can improve TBI-induced ALI.

METHODS

Sprague-Dawley male rats were randomly divided into 3 groups. Except for the sham group (group S), rats were subjected to a fluid percussion injury (FPI) and the H treatment group were given inhaled hydrogen for 1 h per day. We evaluated the lung function, pyroptosis and apoptosis at 24 h, 48 h and 72 h.

RESULTS

Compared with group S, the rats in the TBI group (group T) showed obvious pulmonary edema after a TBI. Inhalation of high-concentration hydrogen significantly improved the rats. During this process, rats had some tendency to heal on their own, and H also accelerated the self-healing process. Lung injury scores, oxygenation index and pulmonary edema were consistent. Compared with group S, the pyroptosis-related proteins Caspase-1, apoptosis-associated speck-like protein containing CARD (ASC) and Gasdermin-D (GSDM-D) in the lung tissues of the rats in group T were significantly increased after a TBI. In the H treatment group (group H), these proteins were significantly decreased. The levels of IL-1β and IL-18 were significantly increased after TBI while in group H were significantly decreased. At the same time, cleaved caspase-3 and BCL-2/Bax were also changed after H treatment. These demonstrates the powerful ameliorating effect of H on pyroptosis, apoptosis and systemic inflammation. However, rats also had tendency to heal on their own, and H also accelerated the self-healing process at the same time.

CONCLUSIONS

H improves TBI-ALI, and the mechanism may be due to the decrease of both pyroptosis and apoptosis and the alleviation of inflammation. These findings provide a reference and evidence for the use of H in TBI-ALI patients in the intensive care unit (ICU).

摘要

背景

创伤性脑损伤（TBI）引起的急性肺损伤（ALI）是一种危急情况，炎症和细胞凋亡起着重要作用。分子氢（H）具有抗炎和抗细胞凋亡作用。我们之前的工作表明，42%的 H 可以改善 TBI。在目前的研究中，我们测试了这样一个假设，即每天吸入 1 小时 42%的 H（21%的 O，平衡氮气）可以改善 TBI 引起的 ALI。

方法

将 Sprague-Dawley 雄性大鼠随机分为 3 组。除假手术组（组 S）外，大鼠均接受液压冲击伤（FPI），H 治疗组每天给予吸入氢 1 小时。我们在 24 小时、48 小时和 72 小时评估肺功能、细胞焦亡和细胞凋亡。

结果

与组 S 相比，TBI 组（组 T）大鼠 TBI 后出现明显肺水肿。吸入高浓度氢气可显著改善大鼠。在此过程中，大鼠有一定的自行愈合趋势，H 也加速了自愈合过程。肺损伤评分、氧合指数和肺水肿一致。与组 S 相比，TBI 后大鼠肺组织中与细胞焦亡相关的蛋白 Caspase-1、凋亡相关斑点样蛋白含 CARD（ASC）和 Gasdermin-D（GSDM-D）明显增加，而在 H 治疗组（组 H）中则明显减少。TBI 后，IL-1β和 IL-18 水平明显升高，而组 H 中则明显降低。同时，H 处理后 cleaved caspase-3 和 BCL-2/Bax 也发生变化。这些表明 H 对细胞焦亡、细胞凋亡和全身炎症具有强大的改善作用。然而，大鼠也有自行愈合的趋势，同时 H 也加速了自愈合过程。