[亚慢性苯并[a]芘暴露对大鼠海马胆碱能系统的影响]
[Effects of subchronic benzo[a]pyrene exposure on hippocampal cholinergic system in rats].
作者信息
Guo Liang, Wang Xin, Li Jin-yan, Liang Hua-shan, Jiang Yong, Chang Shan-shan, Song Yu-jing, Cheng Li, Zheng Jin-ping
机构信息
Department of Toxicology, School Public Health, Shanxi Medical University, Taiyuan 030001, China.
出版信息
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2013 Feb;31(2):108-12.
OBJECTIVE
To observe the effects of subchronic benzo[a]pyrene (B[a]P) exposure on the neurobehavior and hippocampal acetylcholine (Ach) level, acetylcholinesterase (AChE) activity, and mRNA and protein expression of nicotinic acetylcholine receptor α7 subtype (nAChR α7) in rats, and to investigate the neurotoxic mechanism of B[a]P.
METHODS
Sixty healthy male SD rats were randomly divided into blank control group, solvent control group, and B [a]P exposure groups. Each rat in the exposure groups was intraperitoneally injected with B[a]P at 1.0, 2.5, or 6.25 mg/kg once every other day for 90 days. The learning and memory ability of the rats was examined by Morris water maze test and step-down test; the hippocampal Ach level was measured by alkaline hydroxylamine method; the AChE activity was measured by DNTB method; the mRNA and protein expression levels of hippocampal nAChR α7 were measured by quantitative PCR and Western blot.
RESULTS
The 2.5 and 6.25 mg/kg B[a]P exposure groups showed significantly lower learning and memory abilities than the blank control group and solvent control group (P < 0.05); also, the two groups had significantly lower hippocampal Ach levels than the blank control group, solvent control group, and 1.0 mg/kg B[a]P exposure group (P < 0.05). The 6.25 mg/kg B[a]P exposure group showed significantly lower hippocampal AChE activity than the blank control group, solvent control group, and 1.0 mg/kg B[a]P exposure group (P < 0.05). There were no significant differences in the mRNA and protein expression levels of nAChR α7 among all groups (P > 0.05). The hippocampal Ach level was negatively correlated with the mean escape latency period and total distance travelled (r = -0.567, P < 0.01; r = -0.503, P < 0.01) but positively correlated with the time in platform quadrant (r = 0.800, P < 0.01).
CONCLUSION
Subchronic B[a]P exposure may impair the learning and memory ability in rats, which is related to the downregulation of hippocampal Ach level.
目的
观察亚慢性苯并[a]芘（B[a]P）染毒对大鼠神经行为及海马乙酰胆碱（Ach）水平、乙酰胆碱酯酶（AChE）活性、烟碱型乙酰胆碱受体α7亚型（nAChRα7）mRNA和蛋白表达的影响，探讨B[a]P的神经毒性机制。
方法
将60只健康雄性SD大鼠随机分为空白对照组、溶剂对照组和B[a]P染毒组。染毒组大鼠每隔1天腹腔注射1.0、2.5或6.25mg/kg的B[a]P，共90天。采用Morris水迷宫试验和跳台试验检测大鼠的学习记忆能力；用碱性羟胺法测定海马Ach水平；用DNTB法测定AChE活性；用定量PCR和Western blot检测海马nAChRα7的mRNA和蛋白表达水平。
结果
2.5和6.25mg/kg B[a]P染毒组大鼠的学习记忆能力显著低于空白对照组和溶剂对照组（P<0.05）；且这两组海马Ach水平显著低于空白对照组、溶剂对照组和1.0mg/kg B[a]P染毒组（P<0.05）。6.25mg/kg B[a]P染毒组海马AChE活性显著低于空白对照组、溶剂对照组和1.0mg/kg B[a]P染毒组（P<0.05）。各染毒组nAChRα7的mRNA和蛋白表达水平差异均无统计学意义（P>0.05）。海马Ach水平与平均逃避潜伏期和总路程呈负相关（r=-0.567，P<0.01；r=-0.503，P<0.01），与在平台象限停留时间呈正相关（r=0.800，P<0.01）。
结论
亚慢性B[a]P染毒可能损害大鼠的学习记忆能力，这与海马Ach水平下调有关。
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