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N-乙酰半胱氨酸通过纠正凝血功能障碍和酸中毒对大鼠失血性休克合并海水浸泡后器官功能起到保护作用。

N-Acetyl-L-Cysteine Protects Organ Function After Hemorrhagic Shock Combined With Seawater Immersion in Rats by Correcting Coagulopathy and Acidosis.

作者信息

Liu Yiyan, Zhu Yu, Zhang Zisen, Bao Daiqin, Deng Haoyue, Liu Liangming, Li Tao

机构信息

State Key Laboratory of Trauma, Burns and Combined Injury, Department of Shock and Transfusion, Research Institute of Surgery, Army Medical Center, Army Medical University, Chongqing, China.

出版信息

Front Physiol. 2022 Mar 22;13:831514. doi: 10.3389/fphys.2022.831514. eCollection 2022.

DOI:10.3389/fphys.2022.831514
PMID:35392376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8980462/
Abstract

BACKGROUND

The mortality of trauma combined with seawater immersion is higher than that of land injury, however, research on how to treat this critical case and which treatments to adopt is lacking.

METHODS

The effect of the thiol compound, N-acetyl-L-Cysteine (NAC), on survival, acidosis, coagulopathy, vital signs, oxidative stress, and mitochondrial and multi-organ function was assessed in a rat model of hemorrhagic shock combined with seawater immersion (Sea-Shock).

RESULTS

Hemorrhagic shock combined with seawater immersion caused a severe lethal triad: multi-organ impairment, oxidative stress, and mitochondrial dysfunction. NAC (30 mg/kg) with lactated Ringer's (LR) solution (2 × blood volume lost) significantly improved outcomes compared to LR or hetastarch (HES 130/0.4) alone. NAC significantly prolonged survival time to 52.48 ± 30.09 h and increased 72 h survival rate to 11/16 (68%). NAC relieved metabolic acidosis and recovered the pH back to 7.33. NAC also restored coagulation, with APTT, PT, and PT-INR decreased by 109.31, 78.09, and 73.74%, respectively, while fibrinogen level increased 246.23% compared with untreated Sea-Shock. Administration of NAC markedly improved cardiac and liver function, with some improvement of kidney function.

CONCLUSION

The addition of NAC to crystalloid resuscitation fluid alleviated oxidative stress, restored redox homeostasis, and provided multi-organ protection in the rats after Sea-Shock. NAC may be an effective therapeutic measure for hemorrhagic shock combined with seawater immersion.

摘要

背景

创伤合并海水浸泡的死亡率高于陆地损伤,但目前缺乏关于如何治疗这种危急情况以及采用何种治疗方法的研究。

方法

在失血性休克合并海水浸泡(海休克)大鼠模型中,评估硫醇化合物N-乙酰-L-半胱氨酸(NAC)对生存率、酸中毒、凝血功能障碍、生命体征、氧化应激以及线粒体和多器官功能的影响。

结果

失血性休克合并海水浸泡导致严重的致死三联征:多器官损伤、氧化应激和线粒体功能障碍。与单独使用乳酸林格氏液(LR)或羟乙基淀粉(HES 130/0.4)相比,NAC(30 mg/kg)联合LR溶液(2倍失血量)显著改善了预后。NAC显著延长生存时间至52.48±30.09小时,并将72小时生存率提高至11/16(68%)。NAC缓解了代谢性酸中毒,使pH值恢复至7.33。NAC还恢复了凝血功能,与未治疗的海休克相比,活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和国际标准化比值(PT-INR)分别降低了109.31%、78.09%和73.74%,而纤维蛋白原水平增加了246.23%。给予NAC显著改善了心脏和肝脏功能,肾功能也有一定改善。

结论

在晶体复苏液中添加NAC可减轻氧化应激,恢复氧化还原稳态,并为海休克后的大鼠提供多器官保护。NAC可能是治疗失血性休克合并海水浸泡的有效治疗措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/23945fd1672b/fphys-13-831514-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/e1143e62fd33/fphys-13-831514-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/a1d48cc9ad8e/fphys-13-831514-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/d9f21cd4fc5b/fphys-13-831514-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/2e6a4c2b66a6/fphys-13-831514-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/23945fd1672b/fphys-13-831514-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/e1143e62fd33/fphys-13-831514-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/a1d48cc9ad8e/fphys-13-831514-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/d9f21cd4fc5b/fphys-13-831514-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/2e6a4c2b66a6/fphys-13-831514-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c9e/8980462/23945fd1672b/fphys-13-831514-g007.jpg

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