富氢盐水通过抑制异氟烷诱导的氧化应激、线粒体功能障碍以及ATP水平降低，减轻异氟烷诱导的半胱天冬酶-3激活和认知障碍。
Hydrogen-rich saline attenuates isoflurane-induced caspase-3 activation and cognitive impairment via inhibition of isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels.
作者信息
Li Cheng, Hou Lengchen, Chen Dan, Lin Fuqing, Chang Tao, Li Mengzhu, Zhang Lingling, Niu Xiaoyin, Wang Huiying, Fu Shukun, Zheng Junhua
机构信息
Department of Anesthesiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, 200072, China.
Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, 200072, China.
出版信息
Am J Transl Res. 2017 Mar 15;9(3):1162-1172. eCollection 2017.
OBJECTIVES
The inhaled general anesthetic isoflurane has been shown to induce caspase-3 activation in vitro and in vivo. The underlying mechanisms and functional consequences of this activity remain unclear. Isoflurane can induce caspase-3 activation by causing accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and reduction in adenosine triphosphate (ATP) levels. This study aimed to investigate the protective effect of hydrogen, a novel antioxidant, against isoflurane-induced caspase-3 activation and cognitive impairment.
METHODS
H4 human neuroglioma cells overexpressing human amyloid precursor protein were treated with saline or hydrogen-rich saline (HS, 300 μM), with or without 2% isoflurane, for 6 h or 3 h. Western blot analysis, fluorescence assays, and a mitochondrial swelling assay were used to evaluate caspase-3 activation, levels of ROS and ATP, and mitochondrial function. The effect of the interaction of isoflurane (1.4% for 2 h) and HS (5 mL/kg) on cognitive function in mice was also evaluated using a fear conditioning test.
RESULTS
We found that HS attenuated isoflurane-induced caspase-3 activation. Moreover, HS treatment mitigated isoflurane-induced ROS accumulation, opening of mitochondrial permeability transition pores, reduction in mitochondrial membrane potential, and reduction in cellular ATP levels. Finally, HS significantly alleviated isoflurane-induced cognitive impairment in mice.
CONCLUSIONS
Our results suggest that HS attenuates isoflurane-induced caspase-3 activation and cognitive impairment via inhibition of isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. These findings warrant further research into the underlying mechanisms of this activity, and indicate that HS has the potential to attenuate anesthesia neurotoxicity.
目的
吸入性全身麻醉药异氟烷已被证明在体外和体内均可诱导半胱天冬酶 - 3激活。这种活性的潜在机制和功能后果仍不清楚。异氟烷可通过导致活性氧（ROS）积累、线粒体功能障碍和三磷酸腺苷（ATP）水平降低来诱导半胱天冬酶 - 3激活。本研究旨在探讨新型抗氧化剂氢气对异氟烷诱导的半胱天冬酶 - 3激活和认知障碍的保护作用。
方法
将过表达人淀粉样前体蛋白的H4人神经胶质瘤细胞用生理盐水或富氢盐水（HS，300μM）处理，有或无2%异氟烷，处理6小时或3小时。采用蛋白质免疫印迹分析、荧光测定和线粒体肿胀试验来评估半胱天冬酶 - 3激活、ROS和ATP水平以及线粒体功能。还使用恐惧条件试验评估异氟烷（1.4%，2小时）和HS（5 mL/kg）相互作用对小鼠认知功能的影响。
结果
我们发现HS减弱了异氟烷诱导的半胱天冬酶 - 3激活。此外，HS处理减轻了异氟烷诱导的ROS积累、线粒体通透性转换孔开放、线粒体膜电位降低和细胞ATP水平降低。最后，HS显著减轻了异氟烷诱导的小鼠认知障碍。
结论
我们的结果表明，HS通过抑制异氟烷诱导的氧化应激、线粒体功能障碍和ATP水平降低，减弱了异氟烷诱导的半胱天冬酶 - 3激活和认知障碍。这些发现值得对该活性的潜在机制进行进一步研究，并表明HS有减轻麻醉神经毒性的潜力。
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