半夏泻心汤对衰老大鼠学习记忆能力的改善及分子机制
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摘要
目的以D-半乳糖致衰老大鼠为动物模型,研究半夏泻心汤(BXT)对衰老大鼠学习记忆能力的改善及大脑海马区Ach、NE、DA、5-HT受体mRNA表达的影响,探究BXT对改善大鼠学习记忆能力的相关作用机制。方法结合Y型水迷宫测试的大鼠逃避潜伏时间,通过注射D-半乳糖建立老龄大鼠模型;随后将动物分为老龄对照组、石杉碱甲组、壮年对照组、BXT低剂量组、BXT中剂量组、BXT高剂量组,按组别不同进行灌胃给药。连续给药6周后,再次通过Y型水迷宫测试大鼠学习记忆能力改善情况,检测Ach、NE、DA、5-TH受体mRNA及抗体的表达,观察海马区病理学变化,由此探究BXT对衰老大鼠学习记忆能力改善的分子机制。结果与老龄对照组比较,在训练后24 h、48 h和96 h,各剂量BXT给药组均能明显缩短老龄大鼠逃避潜伏期。大鼠海马区组织HE染色显示,与老龄对照组相比,BXT高剂量组海马神经元损伤有所改善,但BXT中剂量组和低剂量组未见明显改善;免疫组化结果显示BXT高剂量组与老龄对照组相比,其椎体细胞染色数量多,排列紧密度好,细胞颜色较深。结论本研究发现BXT能改善老龄大鼠学习记忆能力,尤其是高剂量BXT改善效果最为明显,可能与增加老龄模型大鼠海马CHRM1、DRD2、HTR1a、ADRA2a mRNA的表达有关。
Objective Using D-galactose-induced aging rats as animal model to study the effect of Banxia Xiexin Decoction(BXT) on aged rat's learning and memory ability and the expression of Ach, NE, DA, 5-HT receptor mRNA in the hippocampus of the brain,explore the mechanism of BXT to improve the aged rat's learning and memory ability. Method According to Rat escape latency by Y water maze test,and D-galactose injection to establish aging rat model;Then the animals divided into Aging control group, Huperzine A group, Strong control group, BXT low dose group, BXT medium dose group, BXT high dose group,intragastric administration by different group.After 6 weeks of treatment, the learning and memory abilities of rats were tested by Y-type water maze again,and detect NE, DA, 5-TH receptor mRNA and antibody expression, observe the pathologic changes of hippocampus, therefore explore the molecular mechanism of BXT on aging rat's learning and memory ability. Result The mean escape latency in the Y-type water maze test was shortened in BXT-treated group. The HE staining of the hippocampus showed that the damage of the hippocampus neurons in the high dose BXT group was improved compared with the model control group, but there was no significant improvement in the immunohistochemical result in medium and low dose BXT group. The result of immunohistochemistry showed that the BXT high dose group had more chromosomes than the model control group, and the cells were darker. Conclusion This study found that BXT can improve aging rat's learning and memory ability,especially the high-dose BXT group.The possible machanism is to increase the aging model hippocampus expression of CHRM1, DRD2, HTR1 a, ADRA2 a mRNA.
Objective Using D-galactose-induced aging rats as animal model to study the effect of Banxia Xiexin Decoction(BXT) on aged rat's learning and memory ability and the expression of Ach, NE, DA, 5-HT receptor mRNA in the hippocampus of the brain,explore the mechanism of BXT to improve the aged rat's learning and memory ability. Method According to Rat escape latency by Y water maze test,and D-galactose injection to establish aging rat model;Then the animals divided into Aging control group, Huperzine A group, Strong control group, BXT low dose group, BXT medium dose group, BXT high dose group,intragastric administration by different group.After 6 weeks of treatment, the learning and memory abilities of rats were tested by Y-type water maze again,and detect NE, DA, 5-TH receptor mRNA and antibody expression, observe the pathologic changes of hippocampus, therefore explore the molecular mechanism of BXT on aging rat's learning and memory ability. Result The mean escape latency in the Y-type water maze test was shortened in BXT-treated group. The HE staining of the hippocampus showed that the damage of the hippocampus neurons in the high dose BXT group was improved compared with the model control group, but there was no significant improvement in the immunohistochemical result in medium and low dose BXT group. The result of immunohistochemistry showed that the BXT high dose group had more chromosomes than the model control group, and the cells were darker. Conclusion This study found that BXT can improve aging rat's learning and memory ability,especially the high-dose BXT group.The possible machanism is to increase the aging model hippocampus expression of CHRM1, DRD2, HTR1 a, ADRA2 a mRNA.
引文
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[8] 龚国清,徐黻本.小鼠衰老模型研究[J].中国药科大学学报,1991,22(2):101-103.
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[10] Wilkerson A,Levin E D.Ventral hippocampal dopamine D1 and D2 systems and spatial working menory in rats[J].Neuroscience,1999,89(3):743-749.
[11] 梁发权,吕宝璋.大鼠脑中5-HT受体的检定及其在衰老时的变化[J].中国应用生理学杂志,1991(2):113-116.
[12] 吴小未,王邦安,王萌芽.石杉碱甲增强大鼠海马脑片CA1锥体神经元的兴奋性突触传递[J] .中国临床药理学与治疗学,2012,17(10):1091-1097.
[13] Doralp S, Leung L S. Cholinergic modulation of hippocampal CA1 basal-dendritic long-term potentiation[J]. Neurobiol Learn Mem, 2008, 90(2):382-388.
[14] 赵乔,焦守怒,王钜.阿尔茨海默病动物模型和治疗的相关进展[J].实验动物科学,2009,26(3):39-45.
[15] 李利民,宁楠,刘洁,等.半夏泻心汤对衰老大鼠学习记忆能力及乙酰胆碱酯酶的影响[J].中药药理与临床,2015,(4):9-11.
[16] 白杨,辛随成.阿尔兹海默病动物模型的研究进展[J].实验动物科学,2013,30(6):61-65.
[2] 崔丽君,张艳,郑志娟,等.近六十年半夏泻心汤相关研究文献分析[J].西部中医药,2015,28(7):43-46.
[3] 张吉仲,李利民,黄利,等.半夏泻心汤及其拆方对脾虚大鼠下丘脑中多巴胺、去甲肾上腺素和5-羟色胺的影响[J].华西药学杂志,2014,29(3):286-288.
[4] 渡边泰雄,李璟,刘力,等.半夏泻心汤对水浸拘束诱发大鼠胃溃疡的抑制作用及对脑和胃的单胺调节.汉方最新治疗[J].1997,6(2):167-172.
[5] 张忠,司银楚,吴海霞,等.半夏泻心汤及其拆方对应激性胃溃疡大鼠胆碱能神经元的影响[J].中国中医基础医学杂志,2005,11(4):283-287.
[6] Li Y K.Experimental methodology of TCM pharmacology [M]. Shanghai: Shanghai science and Technology Publishing House, 1986:174.
[7] 朱亚珍,朱虹光.D-半乳糖致衰老动物模型的建立及其检测方法[J].复旦学报(医学版),2007:34(4):617-619.
[8] 龚国清,徐黻本.小鼠衰老模型研究[J].中国药科大学学报,1991,22(2):101-103.
[9] 陈乔,李征峰,李青,等.六味地黄丸对老年大鼠学习记忆及脑内M1胆碱受体阳性神经元的影响[J].中国实验方剂学杂志,2013,19(3):205-208.
[10] Wilkerson A,Levin E D.Ventral hippocampal dopamine D1 and D2 systems and spatial working menory in rats[J].Neuroscience,1999,89(3):743-749.
[11] 梁发权,吕宝璋.大鼠脑中5-HT受体的检定及其在衰老时的变化[J].中国应用生理学杂志,1991(2):113-116.
[12] 吴小未,王邦安,王萌芽.石杉碱甲增强大鼠海马脑片CA1锥体神经元的兴奋性突触传递[J] .中国临床药理学与治疗学,2012,17(10):1091-1097.
[13] Doralp S, Leung L S. Cholinergic modulation of hippocampal CA1 basal-dendritic long-term potentiation[J]. Neurobiol Learn Mem, 2008, 90(2):382-388.
[14] 赵乔,焦守怒,王钜.阿尔茨海默病动物模型和治疗的相关进展[J].实验动物科学,2009,26(3):39-45.
[15] 李利民,宁楠,刘洁,等.半夏泻心汤对衰老大鼠学习记忆能力及乙酰胆碱酯酶的影响[J].中药药理与临床,2015,(4):9-11.
[16] 白杨,辛随成.阿尔兹海默病动物模型的研究进展[J].实验动物科学,2013,30(6):61-65.
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