Fukuda Takasuke, Kakinohana Manabu, Takayama Chitoshi, Matsushita Masayuki, Sugahara Kazuhiro
Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan,
J Anesth. 2015 Aug;29(4):609-17. doi: 10.1007/s00540-014-1968-6. Epub 2015 Jan 8.
Nitrite-derived NO protects against middle cerebral artery occlusion in mice. We developed a new mouse model of global cerebral ischemia and reperfusion (GCI/R) involving reversible occlusion of the major vessels from the aortic arch supplying the brain, and investigated neuroprotection with dietary sodium nitrite supplementation against GCI/R injury.
Mice received drinking water with (nitrite group) or without (control group) sodium nitrite (2 mM) for 5 days and underwent 3-min GCI/R by reversible occlusion of major vessels from the aortic arch (i.e., brachiocephalic, left common carotid, and left subclavian artery). Survival rates and neurological function scores were evaluated for up to 5 days after GCI/R. Histopathological studies were performed to detect neurological degeneration and caspase-3 activation in serial hippocampal sections.
In the control group, 17/30 mice (57 %) survived 5 days after 3-min GCI/R, whereas in the nitrite group 25/30 mice (83 %) survived (p < 0.05). The neurological score at 5 days after GCI in control group was significantly higher than in the nitrite group. Cerebral blood flow (CBF) during GCI was significantly higher in the nitrite group than in the control group, while MABP did not differ significantly between groups. Degenerative changes and caspase-3 activation in hippocampal sections after GCI were observed in the control group but not in the nitrite group. Pretreatment with the NO scavenger c-PTIO abolished the neuroprotective effects of sodium nitrite.
Sodium nitrite supplementation attenuated mortality and neurological impairment after 3-min GCI in mice; an effect likely mediated via vascular mechanisms involving NO.
亚硝酸盐衍生的一氧化氮可保护小鼠免受大脑中动脉闭塞的影响。我们开发了一种新的全脑缺血再灌注（GCI/R）小鼠模型，该模型涉及可逆性闭塞供应大脑的主动脉弓主要血管，并研究了饮食中补充亚硝酸钠对GCI/R损伤的神经保护作用。
小鼠饮用含（亚硝酸盐组）或不含（对照组）亚硝酸钠（2 mM）的水5天，通过可逆性闭塞主动脉弓的主要血管（即头臂干、左颈总动脉和左锁骨下动脉）进行3分钟的GCI/R。在GCI/R后长达5天评估存活率和神经功能评分。进行组织病理学研究以检测连续海马切片中的神经变性和半胱天冬酶-3激活。
在对照组中，17/30只小鼠（57%）在3分钟GCI/R后存活5天，而在亚硝酸盐组中，25/30只小鼠（83%）存活（p<0.05）。对照组GCI后5天的神经评分显著高于亚硝酸盐组。亚硝酸盐组GCI期间的脑血流量（CBF）显著高于对照组，而两组间平均动脉压（MABP）无显著差异。对照组在GCI后海马切片中观察到退行性变化和半胱天冬酶-3激活，而亚硝酸盐组未观察到。用一氧化氮清除剂c-PTIO预处理消除了亚硝酸钠的神经保护作用。
补充亚硝酸钠可降低小鼠3分钟GCI后的死亡率和神经损伤；这种作用可能是通过涉及一氧化氮的血管机制介导的。
