高压氧干预新生大鼠缺氧缺血性脑损伤的时间窗研究被引量：24

Optimal therapeutic window of hyperbaric oxygenation in neonatal rat with hypoxic-ischemic brain damage

导出

摘要目的探讨新生大鼠缺氧缺血性(HI)脑损伤后HBO干预的最佳时间窗。方法84只7日龄SD大鼠随机分为7组:假手术组(sham)、HI组、HI(1h)+HBO组、HI(3h)+HBO组、HI(6h)+HBO组、HI(12h)+HBO组、HI(24h)+HBO组,应用单次高压氧(2.5ATA,1.5h)进行干预。观察大鼠HI后48h皮质区和海马CA1区神经元密度的改变以及大鼠在5周龄的感觉运动功能和6周龄的记忆功能的改变。结果HI后48h,HI(1h)+HBO组、HI(3h)+HBO组、HI(6h)+HBO组3组大鼠皮质区和海马CA1区的神经元密度明显高于HI组(P<0.05);HI(12h)+HBO组和HI(24h)+HBO组与HI组比较差异没有统计学意义(P>0.05)。在5周龄的感觉运动功能测试中,HI(1h)+HBO组、HI(3h)+HBO组、HI(6h)+HBO组3组在握力试验和转杆试验中,各组的抓握时间和停留时间均明显长于HI组(P<0.05);而HI(12h)+HBO组和HI(24h)+HBO组与HIBD组比较,差异没有统计学意义(P>0.05)。在6周龄的记忆功能测试中,HI(1h)+HBO组、HI(3h)+HBO组、HI(6h)+HBO组3组在测试期的跳台潜伏期明显长于HI组(P<0.05),而HI(12h)+HBO组和HI(24h)+HBO组与HI组比较,差异没有统计学意义(P>0.05)。结论单次高压氧(2.5ATA,1.5h)治疗新生大鼠HIBD的最佳时间窗在HIBD后的6h之内。 Objective Hyperbaric oxygenation （HBO） is an attractive procedure that has been used in treatment of hypoxic-ischemlc encephalopathy （HIE）. However, depending on the HBO protocol, espocially the time point of starting treatment of HBO, different and conflicting results were obtained. This study was undertaken to search for the optimal therapeutic window of ABO in neonatal rat with hypoxicischemic brain damage （HIBD）. Methods Eighty-four healthy seven-day-old SD rats were used as research subjects and were randomly divided into seven groups with 12 in each： sham group, HI group, HI（1 h）＋ HBO group（HBO starting 1 h after HI）, HI（3 h）＋HBO group（HBO starting 3 h after HI）, HI（6 h）＋ HBO group（HBO starting 6 h after HI）, HI（12 h）＋HBO group （HBO starting 12 h after HI）, HI（24 h）＋ HBO group （ HBO starting 24 h after HI）. Single HBO treatment （2.5 atmospheres absolute, ATA for 1.5 h） was used in this study. Two indexes were used to assess the effect of HBO that included short-term（48 h after HI） histology change （the cell density in CA1 of hippocampus and cortex） and long-term （5 w and 6 w after HI） neurobehavioral testing （ grip test and treadmill test for evaluating the deficits of sensor motor; step-down avoidance test for assessing the deficits of memory）. Results In HI （1 h）＋HBO, HI（3 h）＋ HBO and HI（6 h）＋ HBO groups, neuron density of cortex and CA1 of hippocampus were 1981.76 ± 299.55, 1841.53±241.21, 1525.78 ± 189. 00 and 4430. 56 ± 1180. 31, 4507. 54 ± 1374. 32, 3883.48 ± 821.87, respectively, which were significantly higher than HIBD group （987. 86 ± 285.39 and 1813.59 ±295.33, P〈0.05, ANOVA）. But in HI （12 h）＋ HBO and HI （24 h）＋HBO, the neuron density of cortex and CA1 of hippocampus compared with those in HIBD group had no statistical significance （P 〉 0. 05, ANOVA）. In the sensor motor testing performed at 5 w after HI of rat, the grip time in grip test and the stay time in treadmill test of HI （ 1 h）＋ HBO, HI （ 3 h）＋ HBO and HI （ 6 h）＋ HBO groups were 193.39±51.19,168. 39 ±34. 02,168. 95±34.93 and 130. 34 ±42. 56, 128. 20±27. 69, 125.74±36. 99, respectively, which, compared with HIBD group, were significantly prolonged （P 〈0. 05, ANOVA）. But in HI （12 h）＋HBO and HI（24 h）＋ HBO groups, the time was not significantly longer compared with HI （P 〉0. 05, ANOVA）. In the step-down avoidance test which was performed at 6 w after HI, the step-down latencies of HI （1 h）＋HBO, HI（3 h）＋HBO and HI（6 h）＋HBO were 96.91±29.91, 90.35 ±28.44 and 76. 46± 38. 70, respectively, which were significantly prolonged （ P 〈 0. 05, ANOVA）, but in HI （ 12 h）＋ HBO and HI（24 h）＋ HBO, the latencies did not significantly increase compared with HIBD,P 〉 0. 05, ANOVA. Conclusions The optimal therapeutic window of HBO in neonatal rat with HIBD was within the first 6 hours after HI. In this therapeutic window, HBO was highly effective in reducing the cell loss in CA1 of hippocampus and cortex.

作者刘小红赵永利马巧梅周熙惠王燕

机构地区西安交通大学医学院第一附属医院儿科

出处《中华儿科杂志》 CAS CSCD 北大核心 2006年第3期177-181,共5页 Chinese Journal of Pediatrics

关键词缺氧缺血脑大鼠高压氧时间生物学 Hypoxia-ischemia,brain Rats Hyperbaric oxygenation Chronobiology

分类号 R722.1 [医药卫生—儿科]

引文网络
相关文献

参考文献14

1Zhang JH,Lo T,Mychaskiw G,et al.Mechanisms of hyperbaric oxygen and neuroprotection in stroke.Pathophysiol,2005,12:63-77.
2Ashwal S,Pearce WJ.Animal models of neonatal stroke.Curr Opin Pediatr,2001,13:506-516.
3Calvert JW,Yin W,Patel M,et al.Hyperbaric oxygenation prevented brain injury induced by hypoxia-ischemia in a neonatal rat model.Brain Res,2002,951:1-8.
4Couturier JY,Ding-Zhou L,Croci N,et al.Grip test-3-Aminobenzamide reduces brain infarction and neutrophil infiltration after transient focal cerebral ischemia in mice.Exp Neurol,2003,184:973-980.
5Wagner BP,Nedelcu J,Martin E.Delayed postischemic hypothermia improves long-term behavioral outcome after cerebral hypoxia-ischemia in neonatal rats.Pediatr Res,2002,51:354-360.
6Tayebi Meybodi K,Vakili Zarch A,Zarrindast MR,et al.Effects of ultra-low doses of morphine,naloxone and ethanol on morphine state-dependent memory of passive avoidance in mice.Behav Pharmacol,2005,16:139-145.
7Ferriero DM.Neonatal brain injury.N Engl J Med,2004,351:1985-1995.
8Badr AE,Yin W,Mychaskiw G,et al.Dual effect of HBO on cerebral infarction in MCAO rats.Am J Physiol Regul Integr Comp Physiol,2001,280:766-770.
9Lou M,Eschenfelder CC,Herdegen T,et al.Therapeutic window for use of hyperbaric oxygenation in focal transient ischemia in rats.Stroke,2004,35:578-583.
10Northington FJ,Ferriero DM,Graham EM,et al.Early neurodegeneration after hypoxia-ischemia in neonatal rat is necrosis while delayed neuronal death is apoptosis.Neurobiol Dis,2001,8:207-219.