氢共同呼吸可以对抗七氟烷新生儿麻醉后脑损伤

Coadministration of Hydrogen Gas as Part of the Carrier Gas Mixture Suppresses N.pdf

对疾病的治疗，从根本上来讲，一般不如预防疾病的发生。例如新生儿窒息后脑损伤，无论采用什么方法，总不如减少窒息的发生。脑外伤最大的因素是交通事故，水平高的医疗救治绝对不如把重点放在减少交通事故的发生率的意义更大。治疗酒精中毒肯定不如避免酗酒来的彻底。我们过去一直研究各种手段治疗和预防新生儿脑损伤，虽然都获得不错的治疗效果。但这些治疗都是在“预先”设计好的治疗程序下才可以有效。我们为了达到效果，在治疗时机上，肯定在损伤发生在早期，在治疗对象上，一般选择相对不十分严重的，但又不可以太轻微。如果疾病模型损伤程度很大，大多数所谓的实验治疗手段都无能为力。设想一下，一个巨大的机体无法承受的损伤因素，水平再高也无法有效治疗。其实在临床上，一个疾病患者是否可以获得满意的治疗效果，最大的前提是这个患者具有可治疗性。可治疗性包括我们对疾病规律的认识，对患者情况的把握，对治疗手段和时机的理想应用等。否则医术是无法获得有效结果的。

这里有一个最近发表在<<麻醉学>>上的研究非常值得关注，至少比那些所谓的重要疾病更有现实价值。麻醉是外科手术最重要的基础，但麻醉本身也可以引起患者的意外和损伤。在治疗疾病的同时，如何减少因治疗引起的相关损伤是非常值得探讨和研究的问题。由于氧化损伤被认为是Sevoflurane麻醉引起的脑损伤的重要原因之一，而氢气具有理想的抗氧化效果，本研究目的是观察在麻醉的同时混合氢气是否可以预防Sevoflurane麻醉引起的脑损伤。本研究采用常规的研究技术，在麻醉气体中混合1.3%的氢（为什么用这个浓度，而不是1%，2%，4%甚至更高浓度？），通过形态学，蛋白分析和行为学研究等分析氢对预防这类损伤的效果。结果发现，氢对该麻醉剂引起的神经细胞凋亡和神经行为学改变具有治疗作用。根据这一研究，可以考虑在临床开展麻醉的吸入气中加入一定浓度的氢，来避免这一类几乎是必然的损伤。

Coadministration of Hydrogen Gas as Part of the Carrier Gas Mixture Suppresses Neuronal Apoptosis and Subsequent Behavioral Deficits Caused by Neonatal Exposure to Sevoflurane in Mice

Yonamine, Ryuji M.D.; Satoh, Yasushi Ph.D.; Kodama, Mitsuyoshi M.D.; Araki, Yoshiyuki M.D.; Kazama, Tomiei M.D., Ph.D.

Background: In animal models, several anesthetics induce widespread increases in neuronal apoptosis in the developing brain with subsequent neurologic deficits. Although the mechanisms are largely unknown, the neurotoxicity may, at least in part, be due to elevated oxidative stress caused by mitochondrial dysfunction. In an investigation of potential therapies that could protect against this type of damage, we studied the effects of molecular hydrogen on anesthetic-induced neurotoxicity in the developing mouse brain.

Methods: Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (< 1.3%) as part of the carrier gas mixture. Apoptosis was evaluated by immunohistochemical staining for cleaved caspase-3 (n = 8-10/group). Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was also performed to examine apoptosis (n = 3-6/group). Oxidative stress was assessed by immunohistochemical staining for 4-hydroxy-2-nonenal (n = 8/group). Long-term memory and social behavior were examined using the fear conditioning test and the sociability test, respectively (n = 18-20/group).

Results: Western blot analysis showed that coadministration of 1.3% hydrogen gas significantly (P < 0.001) reduced the level of neuronal apoptosis to approximately 40% compared with sevoflurane exposure alone. Immunohistochemical analysis showed that hydrogen reduced oxidative stress induced by neonatal sevoflurane exposure. Although neonatal sevoflurane exposure caused impairment in long-term memory and abnormal social behaviors in adulthood, mice coadministered hydrogen gas with sevoflurane did not exhibit these deficits.

Conclusions: Inhalation of hydrogen gas robustly decreased neuronal apoptosis and subsequent cognitive impairments caused by neonatal exposure to sevoflurane.