Cai Jianmei, Kang Zhimin, Liu Kan, Liu WenWu, Li RunPing, Zhang John H, Luo Xu, Sun Xuejun
Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China.
Brain Res. 2009 Feb 23;1256:129-37. doi: 10.1016/j.brainres.2008.11.048. Epub 2008 Nov 27.
Cerebral hypoxia-ischemia (HI) represents a major cause of brain damage in the term newborn. This study aimed to examine the short and long-term neuroprotective effect of hydrogen saline (H(2) saline) using an established neonatal HI rat pup model. Seven-day-old rat pups were subjected to left common carotid artery ligation and then 90 min hypoxia (8% oxygen at 37 degrees C). H(2) saturated saline was administered by peritoneal injection (5 ml/kg) immediately and again at 8 h after HI insult. At 24 h after HI, the pups were decapitated and brain morphological injury was assessed by 2,3,5-triphenyltetrazolium chloride (TTC), Nissl, and TUNEL staining. Acute cell death, inflammation and oxidative stress were evaluated at 24 h by studying caspase-3 activity, MDA measurement as well as Iba-1 immunochemistry in the brain. At 5 weeks after HI, spontaneous activity test and Morris water maze test were conducted. We observed that H(2) saline treatment reduced the caspase activity, MDA, Iba-1 levels, the infarct ratio, and improved the long-term neurological and neurobehavioral functions. H(2) saline has potentials in the clinical treatment of HI and other ischemia-related cerebral diseases.
脑缺氧缺血（HI）是足月儿脑损伤的主要原因。本研究旨在利用已建立的新生HI大鼠幼崽模型，研究氢生理盐水（H₂生理盐水）的短期和长期神经保护作用。7日龄大鼠幼崽接受左侧颈总动脉结扎，然后进行90分钟的缺氧（37℃下8%氧气）。HI损伤后立即腹腔注射（5ml/kg）H₂饱和生理盐水，并在8小时后再次注射。HI后24小时，将幼崽断头，通过2,3,5-三苯基氯化四氮唑（TTC）、尼氏染色和TUNEL染色评估脑形态学损伤。通过研究脑内caspase-3活性、丙二醛（MDA）测定以及Iba-1免疫化学，在24小时时评估急性细胞死亡、炎症和氧化应激。HI后5周，进行自发活动测试和莫里斯水迷宫测试。我们观察到，H₂生理盐水治疗降低了caspase活性、MDA、Iba-1水平、梗死率，并改善了长期神经和神经行为功能。H₂生理盐水在HI及其他缺血相关脑部疾病的临床治疗中具有潜力。
