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腹腔注射乙酰唑胺对大鼠氧惊厥潜伏期的影响

黄俊龙, 练庆林, 蒋春雷, 郭明珠, 孙学军

第二军医大学海军医学系航海医学教研室. 上海 200433

摘要

为探讨脑血流调节与氧惊厥的关系，本研究在复制大鼠氧惊厥模型的基础上，采用行为学方法测定氧惊厥潜伏期， 并测定脑皮质氧化指标丙二醛(maleic dialdehyde, MDA)含量，采用腹腔注射不同剂量脑血管扩张药物乙酰唑胺(acetazolamide, ACZ)，以及联合注射ACZ及其拮抗剂吲哚美辛(indomethacin, IND)后，观察脑血管扩张对氧化状态以及氧惊厥潜伏期的影 响。结果观察到：(1)腹腔注射ACZ (不小于7.5 mg/kg体重)后，氧惊厥潜伏期明显缩短(P<0.05)，剂量越大，缩短越明 显。腹腔注射IND对氧惊厥潜伏期无显著影响。腹腔注射IND (20 mg/kg体重)，30 min后再注射ACZ (7.5 mg/kg体重)，ACZ的氧惊厥潜伏期缩短作用被对抗(P <0.05)。 (2)腹腔注射ACZ 7.5 mg/kg后，与各组相比，6及16 min暴露后，脑组织MDA含量明显增多(P<0.01， P<0.05); 腹腔注射IND对脑皮质MDA含量无显著影响；在预注射IND，再注射ACZ后， MDA含量显著降低(P<0.01, P<0.05)。结果表明，ACZ外周注射加重氧化损伤，缩短氧惊厥潜伏期；而IND可以对抗其 氧惊厥潜伏期缩短作用以及氧化损伤加重作用，碳酸酐酶活力变化很可能是通过影响脑血管状态而影响氧化损伤以及氧惊 厥潜伏期。

关键词： 高压氧; 惊厥; 碳酸酐酶; 乙酰唑胺; 吲哚美辛; 脑血流

Influence of acetazolamide given intraperitoneally on the latency to hyperbaric oxygen-induced convulsion of rats

Huang Junlong, Lian Qinglin, Jiang Chunlei, Guo Mingzhu, Sun Xuejun

Department of Nautical Medicine, Faculty of Naval Medicine, the Second Military Medical University. Shanghai 200433, China

Abstract

The purpose of the present study was to explore the relation between the modulation of cerebral blood flow and the latency of hyperbaric oxygen-induced convulsion. There were two parts in this study. First, the effect of acetazolamide or (and) indomethacin on the latency of hyperbaric oxygen-induced convulsion was observed. Seventy Sprague-Dawley (SD) rats were randomly divided into 7 groups: the acetazolamide 200, 20, 10, 7.5, 5, 2.5 mg/kg body weight and normal saline (NS) group. Forty rats were divided into 5 groups: indomethacin 20, 10, 5, 2.5 mg/kg body weight and NS groups. Another 40 rats were divided into 5 groups which were administered with indomethacin in the dose of 0 mg/kg (NS), 0 mg/kg (NS), 5, 10 and 20 mg/kg body weight. Thirty min later the first group was given NS, and all the other four groups were given acetazolamide with a dose of 7.5 mg/kg body weight. The animals were given acetazolamide or (and) indomethacin intraperitoneally, and 20 min later they were exposed to the pressure of 6 ATA (absolute atmosphere) of pure oxygen. The time from exposure to the onset of seizure (clonic-tonic convulsion) was recorded for each animal according to behavioral observation. Second, the change of maleic dialdehyde (MDA) was measured after acetazolamide and (or) indomethacin treatment. Seventy-two SD rats were randomly divided into 9 groups: Control, 6 and 16 min respectively with NS, acetazolamide, indomethacin, and both acetazolamide and indomethacin group. The dose of acetazolamide was 7.5 mg/kg body weight and the dose of indomethacin was 20 mg/kg body weight. After injection of drugs, the animals were subjected to the pressure of 6 ATA of pure oxygen in respect to its time course group. Then the rats were decapitated and the cerebral cortex was dissected and homogenized. The content of MDA was determined. We found that (1) when the dose of acetazolamide is higher than 7.5 mg/kg, it shortened the latency to hyperbaric oxygen-induced convulsion significantly (P<0.05, P<0.01). There was no significant difference in the latency between every two groups of rats treated with different doses of indomethacin. But when the rats were administered acetazolamide of 7.5 mg/kg body weight after being pretreated with indomethacin of 20 mg/kg body weight, the outbreak of convulsion was put off remarkably (P<0.05). (2) In comparison with the control, the content of MDA in the group treated with acetazolamide increased significantly (P<0.01), but when the rats were treated with both acetazolamide and indomethacin, the content of MDA was reduced significantly both in 6 and 16 min exposure time projects (P<0.05, P<0.01). These results suggest that acetazolamide which dilates the brain arterioles can obviously shorten the latency of hyperbaric oxygen-induced convulsion and aggravate the oxidation of the brain. Indomethacin can resist acetazolamide's effect on the latency and oxidation level when the animals were exposed to the hyperbaric oxygen. The activity of carbonic anhydrase correlates closely with the oxidation injury.

Key words: Hyperbaric oxygen;Convulsion;Carbonic anhydrase;Acetazolamide;Indomethacin;Cerebral blood flow

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引用本文：

黄俊龙, 练庆林, 蒋春雷, 郭明珠, 孙学军. 腹腔注射乙酰唑胺对大鼠氧惊厥潜伏期的影响 [J]. 生理学报 2005; 57 (4): .

Huang Junlong, Lian Qinglin, Jiang Chunlei, Guo Mingzhu, Sun Xuejun. Influence of acetazolamide given intraperitoneally on the latency to hyperbaric oxygen-induced convulsion of rats . Acta Physiol Sin 2005; 57 (4): (in Chinese with English abstract).