高压氧干预新生大鼠缺氧缺血性脑损伤的时间窗研究

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CAl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。

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

OBJECTIVE: Hyperbaric oxygenation (HBO) is an attractive procedure that has been used in treatment of hypoxic-ischemic encephalopathy (HIE). However, depending on the HBO protocol, especially 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 hypoxic-ischemic 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.