益智仁挥发油对东莨菪碱致小鼠学习记忆障碍的改善作用研究
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摘要
目的:考察益智仁挥发油对东莨菪碱诱导的小鼠学习记忆障碍的改善作用。方法:将50只雄性小鼠随机分为正常组、模型组、阳性药物组(盐酸多奈哌齐,3 mg/kg)和益智仁挥发油低、高剂量组(0.5、1 mL/kg),每组10只。除正常组、模型组小鼠灌胃等体积水外,其余组小鼠均灌胃对应药物,连续27 d;自给药第22天起,除正常组小鼠腹腔注射等体积生理盐水外,其余组小鼠均连续6 d腹腔注射氢溴酸东莨菪碱溶液(3 mg/kg)进行造模。末次给药结束后,采用Morris水迷宫实验考察小鼠行为学;采用苏木精-伊红染色法观察小鼠海马组织CA1区神经细胞形态学;检测小鼠海马组织中乙酰胆碱酯酶(AChE)、胆碱乙酰转移酶(ChAT)的活性;检测小鼠海马组织和血清中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性及丙二醛(MDA)的含量。结果:与模型组比较,阳性药物组和益智仁挥发油高剂量组小鼠的逃避潜伏期分别自第2、3天起显著缩短,第Ⅲ象限停留时间、第Ⅲ象限路程百分比和穿台次数均显著延长或增加,首次穿台时间均显著缩短(P<0.05或P<0.01);小鼠海马组织CA1区神经细胞排列较整齐,结构相对正常,核浓染的程度降低;小鼠海马组织中ChAT、SOD、GSH-Px活性和血清中SOD、GSH-Px活性均显著升高,海马组织中AChE活性显著降低,海马组织和血清中MDA含量均显著降低(P<0.05或P<0.01)。益智仁挥发油低剂量组上述指标虽均有改善,但差异均无统计学意义(P>0.05)。结论:益智仁挥发油能显著改善东莨菪碱导致的小鼠学习记忆障碍,其作用机制可能与其调节AChE、ChAT活性来增强胆碱能神经功能及抗氧化损伤有关。
OBJECTIVE: To investigate the improvement effects of volatile oil from the fruit of Alpinia oxyphylla on scopolamine-induced learning and memory impairment in mice. METHODS:50 male Kunming mice were randomly divided normal group,model group,positive drug group(donepezil hydrochloride,3 mg/kg)and volatile oil from the fruit of A. oxyphylla low-dose and high-dose groups(0.5,1 mL/kg),with 10 mice in each group. Except control group and model group were given equivalent water intragastrically,other groups were given relevant medicine intragastrically for consecutive 27 days. Since the 22 nd day of administration, except normal group was given equivalent normal saline, other groups were given Scopolamine hydrobromide solution(3 mg/kg)intraperitoneally for consecutive 6 days. After last medication,Morris water maze test was used to investigate the praxiology of mice. HE staining was used to observe the morphology of neurons in CA1 area of hippocampus in mice. The activities of AChE and ChAT in hippocampus were detected in mice. The activities of SOD and GSH-Px,the content of MDA in hippocampus and serum were also detected. RESULTS:Compared with model group,the escape latencies of mice were shortened significantly in positive drug group and volatile oil from the fruit of A. oxyphylla high-dose group since second and third day,respectively;retention time and distance percentage in the third quadrant,the frequency of crossing platform were prolonged or increased significantly,while the time of initial crossing platform was shortened significantly(P<0.05 or P<0.01). The neurons in the CA1 area of the hippocampus were arranged orderly,with regular cell shape;the degree of nuclear hyperchromasia was reduced. The activities of ChAT,SOD and GSH-Px in hippocampus,the activities of SOD and GSH-Px in serum were increased significantly;the activity of AChE in hippocampus was decreased significantly;while MDA contents in hippocampus and serum were decreased significantly(P<0.05 or P<0.01). There was improvement to some extent but without statistical significance in above indexes of volatile oil from the fruit of A. oxyphylla low-dose group(P>0.05). CONCLUSIONS:The volatile oil from the fruit of A. oxyphylla can ameliorate scopolamine-induced learning and memory impairment by enhancing the function of cholinergic neurons through regulating the activities of AChE and ChAT and resisting oxidation.
OBJECTIVE: To investigate the improvement effects of volatile oil from the fruit of Alpinia oxyphylla on scopolamine-induced learning and memory impairment in mice. METHODS:50 male Kunming mice were randomly divided normal group,model group,positive drug group(donepezil hydrochloride,3 mg/kg)and volatile oil from the fruit of A. oxyphylla low-dose and high-dose groups(0.5,1 mL/kg),with 10 mice in each group. Except control group and model group were given equivalent water intragastrically,other groups were given relevant medicine intragastrically for consecutive 27 days. Since the 22 nd day of administration, except normal group was given equivalent normal saline, other groups were given Scopolamine hydrobromide solution(3 mg/kg)intraperitoneally for consecutive 6 days. After last medication,Morris water maze test was used to investigate the praxiology of mice. HE staining was used to observe the morphology of neurons in CA1 area of hippocampus in mice. The activities of AChE and ChAT in hippocampus were detected in mice. The activities of SOD and GSH-Px,the content of MDA in hippocampus and serum were also detected. RESULTS:Compared with model group,the escape latencies of mice were shortened significantly in positive drug group and volatile oil from the fruit of A. oxyphylla high-dose group since second and third day,respectively;retention time and distance percentage in the third quadrant,the frequency of crossing platform were prolonged or increased significantly,while the time of initial crossing platform was shortened significantly(P<0.05 or P<0.01). The neurons in the CA1 area of the hippocampus were arranged orderly,with regular cell shape;the degree of nuclear hyperchromasia was reduced. The activities of ChAT,SOD and GSH-Px in hippocampus,the activities of SOD and GSH-Px in serum were increased significantly;the activity of AChE in hippocampus was decreased significantly;while MDA contents in hippocampus and serum were decreased significantly(P<0.05 or P<0.01). There was improvement to some extent but without statistical significance in above indexes of volatile oil from the fruit of A. oxyphylla low-dose group(P>0.05). CONCLUSIONS:The volatile oil from the fruit of A. oxyphylla can ameliorate scopolamine-induced learning and memory impairment by enhancing the function of cholinergic neurons through regulating the activities of AChE and ChAT and resisting oxidation.
引文
[1]中国科学院《中国植物志》编辑委员会.中国植物志:第6卷:第2分册[M].北京:科学出版社,1981:67.
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[5]MITI?-CULAFI?D,ZEGURA B,NIKOLI?B,et al.Protective effect of linalool,myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cell[J].Food Chem Toxicol,2009,47(1):260-266.
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[7]杨久山,孙秀萍,王忆杭,等.连翘酯苷对东莨菪碱模型小鼠学习记忆的影响及其机制研究[J].中国实验方剂学杂志,2016,22(8):177-181.
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[9]JAIN NK,PATIL CS,KULKARNI SK,et al.Modulatory role of cyclooxygenase inhibitors in aging-and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice[J].Behav Brain Res,2002,133(2):369-376.
[10]WEINBERBERGER NM,MIASNIKOV AA,CHEN JC.Sensory memory consolidation observed:increased specificity of detail over days[J].Neurobiol Learn Mem,2009,91(3):273-286.
[11]王爱梅,耿若君,李戈,等.旱莲草对老年痴呆模型大鼠学习记忆及海马神经递质的影响[J].中国中医基础医学杂志,2016,22(3):332-335.
[12]MARKESBERY WR,LOVELL MA.Damage to lipids,proteins,DNA,and RNA in mild cognitive impairment[J].Arch Neurol,2007,64(7):954-956.
[13]FAN Y,HU J,LI J,et al.Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms[J].Neurosci Lett,2005,374(3):222-226.
[14]GOVERDHAN P,SRAVANTHI A,MAMATHA T.Neuroprotective effects of meloxicam and selegiline in scopolamine-induced cognitive impairment and oxidative stress[J].Int J Alzheimers Dis,2012.DOI:10.1155/2012/974013.
[15]DRINGEN R.Metabolism and functions of glutathione in brain[J].Prog Neurobiol,2000,62(6):649-671.
[16]HALL ED,ANDRUS PK.Measurement of oxygen radicals and lipid peroxidation in neural tissues[M].2009.DOI:10.1002/0471142301.ns0717s48.
[2]SHIN TY,WON JH,KIM HM,et al.Effect of Alpinia oxyphylla fruit extract on compound 48/80-induced anaphylactic reactions[J].Am J Chin Med,2001,29(2):293-302.
[3]钟恒亮,王荔萍,陈力.益智仁口服液镇静催眠作用实验研究[J].贵阳医学院学报,2002,27(2):132-134.
[4]黄凌,朱毅,邝少轶.益智仁挥发油抗帕金森模型小鼠黑质神经元凋亡的作用研究[J].中国药房,2011,22(47):4430-4433.
[5]MITI?-CULAFI?D,ZEGURA B,NIKOLI?B,et al.Protective effect of linalool,myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cell[J].Food Chem Toxicol,2009,47(1):260-266.
[6]李生茂,彭璐,夏青,等.益智盐炙前后挥发油化学成分及抗氧化活性的比较研究[J].中医药信息,2015,32(6):23-27.
[7]杨久山,孙秀萍,王忆杭,等.连翘酯苷对东莨菪碱模型小鼠学习记忆的影响及其机制研究[J].中国实验方剂学杂志,2016,22(8):177-181.
[8]王红利,薛莉君,万东,等.梓醇改善东莨菪碱诱导的学习记忆障碍及机制研究[J].中国药理学通报,2011,27(9):1271-1275.
[9]JAIN NK,PATIL CS,KULKARNI SK,et al.Modulatory role of cyclooxygenase inhibitors in aging-and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice[J].Behav Brain Res,2002,133(2):369-376.
[10]WEINBERBERGER NM,MIASNIKOV AA,CHEN JC.Sensory memory consolidation observed:increased specificity of detail over days[J].Neurobiol Learn Mem,2009,91(3):273-286.
[11]王爱梅,耿若君,李戈,等.旱莲草对老年痴呆模型大鼠学习记忆及海马神经递质的影响[J].中国中医基础医学杂志,2016,22(3):332-335.
[12]MARKESBERY WR,LOVELL MA.Damage to lipids,proteins,DNA,and RNA in mild cognitive impairment[J].Arch Neurol,2007,64(7):954-956.
[13]FAN Y,HU J,LI J,et al.Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms[J].Neurosci Lett,2005,374(3):222-226.
[14]GOVERDHAN P,SRAVANTHI A,MAMATHA T.Neuroprotective effects of meloxicam and selegiline in scopolamine-induced cognitive impairment and oxidative stress[J].Int J Alzheimers Dis,2012.DOI:10.1155/2012/974013.
[15]DRINGEN R.Metabolism and functions of glutathione in brain[J].Prog Neurobiol,2000,62(6):649-671.
[16]HALL ED,ANDRUS PK.Measurement of oxygen radicals and lipid peroxidation in neural tissues[M].2009.DOI:10.1002/0471142301.ns0717s48.