高压氧对缺氧缺血性脑损伤新生大鼠脑皮质线粒体生物合成的影响

Hyperbaric oxygenation promotes mitochondrial biogenesis in cerebral cortex of neonatal rats after hypoxic ischemic brain damage

目的观察高压氧对缺氧缺血性脑损伤新生大鼠脑皮质线粒体生物合成的影响及其相关信号通路。方法新生7日龄Wistar大鼠48只随机分为假手术组(Sham,16只),HIBD模型组(HIBD,16只)和高压氧治疗HIBD组(HBO+HIBD,16只)。结扎左侧颈总动脉后暴露于92%氮气和8%氧气缺氧环境中2 h制备HIBD模型。HIBD+HBO组在缺氧缺血后给予高压氧干预,每次持续90 min,每日1次,连续7 d。末次高压氧干预后24 h,每组动物随机抽取8只处死,检测脑皮质COXⅣ、PGC-1α、Tfam和NRF1表达。剩余动物饲养至40日龄进行Morris水迷宫检测。结果 HBO+HIBD组与HIBD组比较,逃避潜伏期显著缩短[(21.49±3.77)s vs(42.50±6.46)s,P<0.01],穿越平台次数、COXⅣ、PGC-1α、Tfam和NRF1表达均显著升高[分别为(7.41±1.13)次vs(5.26±0.78)次,(82.15±14.84)k Pa vs(62.83±11.02)k Pa,(112.19±18.41)k Pa vs(67.26±10.40)k Pa,(92.15±13.99)k Pa vs(76.40±9.32)k Pa和(72.29±12.88)k Pa vs(49.28±7.14)k Pa,P<0.05~0.01]。结论高压氧可通过上调PGC-1过-NRF1/Tfam通路促进脑皮质线粒体生物合成,从而改善大鼠HIBD后空间学习记忆能力。

Objective To observe the effect of hyperbaric oxygenation on mitochondrial biogenesis and related signal pathways in the cerebral cortex of neonatal rats after hypoxic ischemic brain damage. Methods Forty-eight 7-day postnatal Wistar rats were randomly divided into 3 groups： sham operation group（ Sham,n = 16）,hypoxic-ischemic brain damage group（ HIBD,n = 16） and hyperbaric oxygenation treated group（ HBO ＋ HIBD,n = 16）. An HIBD model was established via ligation of the right common carotid artery followed by hypoxia exposure（ 8% O2＋ 92% N2） for two hours. In HBO ＋ HIBD group,rats received hyperbaric oxygenation（ 90 min a day,for 7 consecutive days） after HIBD. Eight rats in each group were sacrificed at 24 h after HBO,and the cerebral cortex was used to detect the expressions of COXⅣ,PGC-1α,Tfam and NRF1. Other rats were tested with Morris water maze at 40 days old.Results As compared with HIBD group,the escape latency in HBO ＋ HIBD group was obviously shorter（ 21. 49 ± 3. 77 vs 42. 50 ±6. 46,P〈0. 01）. The number of times of crossing the platform and the expressions of COXⅣ,PGC-1α,Tfam,and NRF1 were significantly increased（ 7. 41 ± 1. 13 vs 5. 26 ± 0. 78,82. 15 ± 14. 84 vs 62. 83 ± 11. 02,112. 19 ± 18. 41 vs 67. 26 ± 10. 40,92. 15 ± 13. 99 vs 76. 40 ± 9. 32,and 72. 29 ± 12. 88 vs 49. 28 ± 7. 14,respectively,P〈0. 05 - 0. 01）. Conclusions Hyperbaric oxygenation can ameliorate spatial learning and memory impairment in neonatal rats after HIBD. The protective mechanism of HBO may be related to the promotion of PGC-1 a-NRF1/Tfam mediated mitochondrial biogenesis in the cerebral cortex.