益气化痰活血方对SCH大鼠海马记忆能力及ERK1/2-CREB信号通路的影响
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摘要
目的:研究益气化痰活血方对亚临床甲状腺功能减退症(SCH)大鼠记忆影响并探讨可能机制。方法:Wistar大鼠采用"甲状腺全切+左旋甲状腺素(L-T4)皮注"建模,随机分假手术组、模型组、中药组(益气化痰活血方13.7g/kg)、西药组(L-T4 4.5μg/kg)、中西药组。给药6周后行水迷宫测试,后处死取标本检测,放射免疫(RIA)测血清总甲状腺素(TT4),免疫化学发光(ICMA)测血清促甲状腺激素(TSH),RT-PCR测海马ERK1/2、RSK、CREB mRNA表达。结果:模型组巡航时间及探索次数、海马ERK1/2、RSK、CREB mRNA积分光密度值,与假手术组比较,差异有统计学意义(P<0.01);各治疗组巡航时间减少、探索次数增加、ERK1/2、RSK、CREBmRNA积分光密度值显著增加(P<0.01,P<0.05),中西药组优于中药组及西药组(P<0.01,P<0.05)。结论:益气化痰活血方能改善SCH大鼠学习记忆能力,可能与上调海马ERK1/2-CREB通路有关。
Objective: To study the effects of Chinese medicine on memory in SCH rats and explore the possible mechanism. Methods: Wistar rats were modeled with total thyroidectomy and L-T4 hypodermic injection. All rats were randomly divided into sham operation group, model group, Chinese medicine group(Yiqi Huatan Huoxue Formula, 13.7 g/kg),western medicine group(L-T4, 4.5μg/kg), Chinese and western medicine group. Six weeks after administration, water maze test was performed, and then samples were sacrificed. TT4 was measured by radioimmunoassay(RIA), TSH were measured by chemiluminescence immunoassay(ICMA), ERK1/2, RSK and CREB expressions in hippocampus were measured by RT-PTC.Results: The cruise time and exploration times, mRNA integral optical density values of ERK1/2, RSK, CREB in model group were significantly different from those in sham operation group(P<0.01). In each treatment group, the cruise time decreased,exploration times increased, mRNA integral optical density values of ERK1/2, RSK, CREB increased(P<0.01, P<0.05), the Chinese and western medicine group was better than Chinese medicine group and western medicine group(P<0.01, P<0.05).Conclusion: Yiqi Huatan Huoxue Formula can improve the learning and memory ability of SCH rats, which may be related to the up-regulation of ERK1/2-CREB pathway in hippocampus.
Objective: To study the effects of Chinese medicine on memory in SCH rats and explore the possible mechanism. Methods: Wistar rats were modeled with total thyroidectomy and L-T4 hypodermic injection. All rats were randomly divided into sham operation group, model group, Chinese medicine group(Yiqi Huatan Huoxue Formula, 13.7 g/kg),western medicine group(L-T4, 4.5μg/kg), Chinese and western medicine group. Six weeks after administration, water maze test was performed, and then samples were sacrificed. TT4 was measured by radioimmunoassay(RIA), TSH were measured by chemiluminescence immunoassay(ICMA), ERK1/2, RSK and CREB expressions in hippocampus were measured by RT-PTC.Results: The cruise time and exploration times, mRNA integral optical density values of ERK1/2, RSK, CREB in model group were significantly different from those in sham operation group(P<0.01). In each treatment group, the cruise time decreased,exploration times increased, mRNA integral optical density values of ERK1/2, RSK, CREB increased(P<0.01, P<0.05), the Chinese and western medicine group was better than Chinese medicine group and western medicine group(P<0.01, P<0.05).Conclusion: Yiqi Huatan Huoxue Formula can improve the learning and memory ability of SCH rats, which may be related to the up-regulation of ERK1/2-CREB pathway in hippocampus.
引文
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[10]杨瑞霞,陈如泉.温肾方对亚临床甲状腺功能减退模型大鼠心肌组织T3及甲状腺激素受体的影响.中医学报,2013,28(7):989-991
[11]黄婧,郭天康,刘静,等.亚临床甲状腺功能减退大鼠骨代谢改变及左旋甲状腺素效.中华骨质疏松和骨矿盐疾病杂志,2015,8(1):43-47
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[2]聂晓璐,吕晓珍,卓琳,等.2001-2015年中国轻度认知功能障碍患病率的Meta分析.中华精神科杂志,2016,49(5):298-306
[3]Daniele C,Thomas R,Herbert S.Effect of early thyroxine treatment on brain-derived neurotrophic factor mRNA expression and protein amount in the rat medial septum/diagonal band of Broca.Neurosci Lett,2003,350(3):141-144
[4]Ge J F,Xu Y Y,Li N,et al.Resveratrol improved the spatial learning and memory in subclinical hypothyroidism rat induced by hemithyroid electrocauterization.Endocrine Journal,2015,62(10):927-938
[5]郑晖,马光瑜,付晓春.帕罗西汀对抑郁模型大鼠空间学习记忆和海马ERK-CREB通路的效应.中国药学杂志,2008,43(16):1234-1238
[6]庞妍,杨敬华,刘秋芳,等.妊娠期至生长发育期氯化镧暴露致仔鼠学习记忆能力的损伤及对海马ERK/CREB信号转导通路的抑制作用.环境与健康杂志,2013,30(6):471-474
[7]陈巍,高天舒.益气化痰活血方对中青年亚临床甲减致认知功能损伤患者疗效观察.辽宁中医杂志,2017,44(6):1219-1221
[8]朱帅俊.亚临床甲状腺功能减退症动物模型的建立.沈阳:中国医科大学,2008
[9]潘立文.温肾方对亚临床甲减雌鼠血清甲状腺功能的影响.湖北中医杂志,2011,33(10):20-21
[10]杨瑞霞,陈如泉.温肾方对亚临床甲状腺功能减退模型大鼠心肌组织T3及甲状腺激素受体的影响.中医学报,2013,28(7):989-991
[11]黄婧,郭天康,刘静,等.亚临床甲状腺功能减退大鼠骨代谢改变及左旋甲状腺素效.中华骨质疏松和骨矿盐疾病杂志,2015,8(1):43-47
[12]Nunez J.Morris Water Maze Experiment(2008).JOVE.2008,19.http://www.jove.com/index/Details.stp?ID=897.DOI:10.3791/897.
[13]杨婵,杨嫱妃,董文然,等.温肾补虚方对甲减大鼠下丘脑-垂体-甲状腺轴的影响.中华中医药杂志,2017,32(8):3742-3745