CAJ | 학술논문

目的通过观察亚慢性染毒苯并[a]芘(B[a]P)对大鼠神经行为及海马组织中乙酰胆碱(Ach)含量、胆碱酯酶(AChE)活力和乙酰胆碱受体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.方法选择60只健康雄性SD大鼠,随机分为空白对照组,溶剂对照组,1.0、2.5、6.25 mg/kg B[a]P染毒组,隔日腹腔注射连续染毒90 d.Morris水迷宫和跳台试验检测大鼠学习记忆能力.碱性羟胺法检测海马组织Ach含量,DNTB法检测AChE活力.荧光定量PCR和Western-blot法分别检测海马组织nAChRα7 mRNA和蛋白表达水平.结果 Morris水迷宫、跳台试验结果显示,2.5、6.25 mg/kg B[a]P组大鼠学习记忆能力比空白和溶剂对照组大鼠明显下降,差异有统计学意义(P＜0.05).2.5、6.25 mg/kgB[a]P组大鼠海马组织Ach含量明显低于空白、溶剂对照和1.0 mg/kg B[a]P组,差异有统计学意义(P＜0.05),6.25 mg/kg B[a]P组AChE活力明显低于空白对照、溶剂对照和1.0 mg/kg B[a]P组,差异有统计学意义(P＜0.05).各组之间nAChRα7 mRNA和蛋白表达水平的差异无统计学意义(P＞0.05).大鼠海马组织Ach含量与大鼠平均逃避潜伏期和总路程呈负相关(相关系数r分别为-0.567和-0.503,P＜0.01),与平台象限滞留时间呈正相关(r=0.800,P＜0.01).结论亚慢性染毒B[a]P可损伤大鼠学习记忆功能,其机制与大鼠海马组织Ach含量下降有关
목적 통과관찰아만성염독분병[a]비(B[a]P)대대서신경행위급해마조직중을선담감(Ach)함량、담감지매(AChE)활력화을선담감수체α7아형(nAChRα7)mRNA화단백표체적영향,탐토B[a]P적신경독성궤제.방법 선택60지건강웅성SD대서,수궤분위공백대조조,용제대조조,1.0、2.5、6.25 mg/kg B[a]P염독조,격일복강주사련속염독90 d.Morris수미궁화도태시험검측대서학습기억능력.감성간알법검측해마조직Ach함량,DNTB법검측AChE활력.형광정량PCR화Western-blot법분별검측해마조직nAChRα7 mRNA화단백표체수평.결과 Morris수미궁、도태시험결과현시,2.5、6.25 mg/kg B[a]P조대서학습기억능력비공백화용제대조조대서명현하강,차이유통계학의의(P＜0.05).2.5、6.25 mg/kgB[a]P조대서해마조직Ach함량명현저우공백、용제대조화1.0 mg/kg B[a]P조,차이유통계학의의(P＜0.05),6.25 mg/kg B[a]P조AChE활력명현저우공백대조、용제대조화1.0 mg/kg B[a]P조,차이유통계학의의(P＜0.05).각조지간nAChRα7 mRNA화단백표체수평적차이무통계학의의(P＞0.05).대서해마조직Ach함량여대서평균도피잠복기화총로정정부상관(상관계수r분별위-0.567화-0.503,P＜0.01),여평태상한체류시간정정상관(r=0.800,P＜0.01).결론 아만성염독B[a]P가손상대서학습기억공능,기궤제여대서해마조직Ach함량하강유관
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 rng/kg B[a]P exposure group showed significantly lower hippocarnpal 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.