摘要
目的探讨慢性低氧高二氧化碳模型大鼠记忆障碍是否与脑内胆碱能系统变化有关。方法将48只SD大鼠用随机数字表法分为对照组、低氧高二氧化碳2周组、低氧高二氧化碳4周组，每组各16只。建立慢性低氧高二氧化碳大鼠模型，八臂迷宫检测大鼠记忆能力，HE染色和尼氏染色观察海马形态，比色法检测海马乙酰胆碱含量、乙酰胆碱酯酶（AChE）活性、胆碱乙酰转移酶（ChAT）活性，蛋白质印迹法检测海马烟碱型乙酰胆碱受体（nAChR）胡亚型（胡nAChR）蛋白表达。结果与对照组相比，2周组大鼠记忆能力下降，以工作记忆损害为主；与2周组相比，4周组大鼠记忆能力下降。对照组、2周组、4周组海马ChAT活性分别为（127．1±8．6）U／g（组织湿重）、（90．4±6．9）U／g（组织湿重）和（55．6±6．0）U／g（组织湿重）；AChE活性分别为（0．326±0．019）U／mg（蛋白）、（0．247±0．020）U／mg（蛋白）和（0．170±0．019）U／mg（蛋白）；ACh含量分别为（58．9±2．7）μg／mg（蛋白）、（47．4±3．2）μg／mg（蛋白）和（32．5±3．2）μg／mg（蛋白）。与对照组相比，2周组大鼠海马ChAT活性及AChE活性下降，ACh含量减少，差异均有统计学意义（t=9．408、8．139、7．674，均P〈0．05）；与2周组相比，4周组大鼠海马ChAT活性及AChE活性下降，ACh含量减少，差异均有统计学意义（t=10．781、8．036、9．279，均P〈0．05）。蛋白质印迹显示海马胡nAChR蛋白表达2周组较对照组减少，4周组较2周组减少，差异均有统计学意义。结论长期暴露于低氧高二氧化碳环境导致大鼠记忆能力下降，暴露时间越长损害越明显，海马胆碱能系统的功能失调可能是其记忆障碍的原因之一。
Objective To investigate the relationship between changes of cholinergic system and memory ability impairment in rats long-term exposed to hypoxia-hypercapnia. Methods Forty-eight SD rats were randomly divided into control group, 2 weeks hypoxia-hypercapnia group and 4 weeks hypoxia- hypercapnia group. The chronic hypoxia-hypercapnia rat model was set up. The memory ability was assessed by eight-arm radial maze. Morphological changes were observed by the HE staining and Nissl staining. Acetylcholine（ ACh ） content, choline acetyl-transferase （ ChAT ） activity and acetyl-cholinesterase （ AChE ） activity in the hippocampus were detected by spectrophotometry, while expression of or7 neuronal nicotinic acetylcholine receptor （or7 nAChR ） protein by Western blot. Results Memory ability, especially the working memory was impaired in rats exposed to chronic hypoxia-hypereapnia. And the memory ability decreased more markedly in four weeks group. Compared with those of normoxic rats, the levels of ACh and the activities of AChE and ChAT in the hippocampus of the two weeks group were significantly decreased （ACh： （58. 9 ±2. 7） vs （47. 4 ±3.2） μg/mg （protein） ; ACHE： （0. 326 ±0. 019） vs （0. 247 ±0. 020） U/mg （protein） ; ChAT： （ 127.1 ± 8.6） vs （90.4 ± 6. 9 ） U/g （ tissue wet weight）, t = 7. 674, 8. 139, 9. 408, all P 〈 0.05）. Compared with the two weeks group, those changes were more obvious in the four weeks group rats （ ACh ： （47.4 ± 3.2 ） vs （ 32. 5 ± 3.2 ） txg/mg （protein） ; AChE ： （0. 247 ± 0. 020 ）, （0. 170 ±0. 019） U/mg （protein） ; CHAT： （90. 4±6. 9）, （55.6 ±6.0） U/g （tissue wet weight）, t =9. 279, 8.036, 10. 781, all P 〈 0. 05）. Compared with the normoxic rats, the expressions of 0-7 nAChR protein were significantly decreased in two weeks group rats （ t = 4. 481, P 〈 0. 05 ）. Moreover, the expressions of et7 nAChR protein were significantly decreased in four weeks group rats comparing with the two weeks group （ t = 4. 965, P 〈 0.05）. Conclusions An impairment of rat＇ s memory ability may be induced by hypoxia-hypercapnia, and the injury degree is correlated with the exposure time. Cholinergic system dysfunctions may contribute to the memory function defects in chronic hypoxia-hypercapnia rats.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2013年第1期47-50,共4页
Chinese Journal of Neurology
基金
浙江省自然科学基金资助项目（Y205233）
温州市科技局资助项目（Y2005A001）
关键词
缺氧
高碳酸血
记忆障碍
乙酰胆碱
受体
胆碱能
大鼠
Anoxia
Hypercapnia
Memory disorders
Acetylcholine
Receptors, cholinergic
Rats
