亚临床甲状腺功能异常对小鼠Morris水迷宫实验中学习记忆行为的影响Effects of subclinical thyroid function status on rat of learning and memory behavior in Morris water maze
詹璐,闫桂玲,胡薇
摘要(Abstract):
目的建立亚临床甲状腺功能亢进和减退2种不同甲状腺功能状态的小鼠模型,并明确亚临床甲状腺功能水平不同对小鼠Morris水迷宫实验中学习记忆行为的影响。方法选取30只Balb/C雄性小鼠,周龄5~6周,适应性饲养1周后,随机分为亚甲亢组、亚甲减组和对照组,每组10只。经高、低剂量摸索后确定造模用药剂量。观察3组小鼠对声、光等外界刺激的反应。3周后行Morris水迷宫实验,对比分析3组小鼠行为学差异。同时采集血清标本验证是否造模成功。结果亚甲亢组小鼠每日给予腹腔注射优甲乐25μg/100 g鼠重,亚甲减组每日给予小鼠腹腔注射甲巯咪唑(MMI)1.5 mg/100g鼠重,对照组常规喂养。亚甲亢组促甲状腺激素(TSH)为(0.27±0.09)mU/L,亚甲减组TSH为(3.15±0.68)mU/L,对照组TSH为(1.01±0.16)mU/L,3组差异有统计学意义(P<0.01),三碘甲状腺原氨酸(T3)、甲状腺素(T4)差异无统计学意义(P>0.05)。3组小鼠天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平差异无统计学意义(P>0.05)。定位航行实验,与对照组相比,亚甲亢组每日逃避潜伏期明显缩短(P<0.05),分别为(68±29)s、(51±36)s、(41±39)s、(38±41)s,而亚甲减组差异无统计学意义(P>0.05)。空间探索实验,亚甲亢组目标象限路程比为(29±16)%,亚甲减组为(14±11)%,对照组为(15±11)%,亚甲亢组目标象限时间比为(33±20)%,亚甲减组为(15±14)%,对照组为(17±12)%,亚甲亢组穿台次数为2.0(1.75,3.0)次,亚甲减组为1.0(0,1.0)次,对照组为1.0(0.75,1.0)次。亚甲亢组3组指标均显著高于对照组(P<0.05),而亚甲减组差异无统计学意义(P>0.05)。3组平均速度差异无统计学意义(P>0.05)。结论运用优甲乐和甲巯咪唑腹腔注射的方法可成功建立亚甲亢和亚甲减小鼠动物模型。通过Morris水迷宫实验发现亚甲亢组小鼠的空间学习、记忆能力比对照组小鼠增强,而亚甲减组小鼠无明显差异。
关键词(KeyWords): 认知;小鼠;亚临床甲状腺功能异常;Morris水迷宫实验
基金项目(Foundation): 上海长海医院院级科研项目(军事医学专项)(2018JS011);上海长海医院教学研究与改革项目(CHJG2019018)
作者(Author): 詹璐,闫桂玲,胡薇
参考文献(References):
- [1]刘婷婷,滕卫平.中国国民碘营养现状与甲状腺疾病[J].中华内科杂志,2017,56(1):62-64.
- [2]Antonelli A,Ferrari SM,F Ragusa,et al.Graves′disease:epidemiology,genetic and environmental risk factors and viruses[J].Best Pract Res Clin,2020,34(1):101387:1-17.
- [3]Fahrenfort JJ,Wilterdink AM,Ea VDV.Long-term residual complaints and psychosocial sequelae after remission of hyperthyroidism[J].Psychoneuroendocrinol,2000,25(2):201-211.
- [4]Gulseren S,Gulseren L,Hekimsoy Z,et al.Depression,anxiety,health-related quality of life,and disability in patients with overt and subclinical thyroid dysfunction[J].Arch Med Res,2006,37(1):133-139.
- [5]Wouters H,Loon HV,Van D,et al.No effect of the Thr92Ala polymorphism of deiodinase-2 on thyroid hormone parameters,health-related quality of life and cognitive functioning in a large population-based cohort study[J].Thyroid,2017,27 (2):147-155.
- [6]Hu Y,Wang ZC,Guo QH,et al.Is thyroid status associatedwith cognitive impairment in elderly patients in China?[J].BMCEndocr Disord,2016,16 (11):1-7.
- [7]Aubert CE,Bauer DC,Da Costa BR,et al.The association between subclinical thyroid dysfunction and dementia:the health,aging and body cmposition (Health ABC) study[J].Clin Endocrinol (Oxf),2017,87(5):617-626.
- [8]G?bel A,G?ttlich M,Heldmann M,et al.Experimentally induced subclinical hypothyroidism causes decreased functional connectivity of the cuneus:a resting state f MRI study[J].Psychoneuroendocrinol,2019,102:158-163.
- [9]Ojala AK,Schalin-J?ntti C,Pitk?l?KH,et al.Serumthyroid stimulating hormone and cognition in older people[J].Age Ageing,2016,45(1):155-157.
- [10]Li Y,Teng D,Ba J,et al.Efficacy and safety of longterm universal salt iodization on thyroid disorders:epidemiological evidence from 31 provinces of mainland China[J].Thyroid,2020,30(4):568-579.
- [11]朱帅俊.亚临床甲状腺功能减退症动物模型的建立[D].沈阳:中国医科大学,2008.
- [12]廖虹,文建华.温肾方对亚临床甲状腺功能减退症大鼠模型甲状腺功能和血脂的影响[J].四川中医,2010,28(12):16-17.
- [13]鲁丽,王红,张红梅,等.妊娠早期左旋甲状腺素治疗亚临床甲减母鼠可改善仔鼠神经智力发育[J].中华内分泌代谢杂志,2010,26(11):942-947.
- [14]张立亚,贾雯羽,许云云,等.小鼠亚临床甲状腺功能减退模型脂代谢相关micro RNAs表达的变化[J].中华内分泌代谢杂志,2018,34(5):410-415.
- [15]陈巍,高天舒,张凤暖,等.甲巯咪唑致亚临床甲减大鼠模型评价[J].长春中医药大学学报,2017,33(1):43-46.
- [16]Morris R.Spatial localization does not require the presence of localcues[J].Learn Motiva,1981,12(2):239-260.
- [17]王俊亚,张冬梅.Morris水迷宫实验的测试方法介绍及注意事项[J].现代医药卫生,2012,28(21):3289-3290.
- [18]邱宏,金国琴,金如锋,等.水迷宫重复测量数据的方差分析及其在SPSS中的实现[J].中西医结合学报,2007,5(1):101-105.
- [19]Meneses A.5-HT systems:emergent targets for memory formation and memory alterations[J].Rev Neurosciences,2013,24(6):629-664.
- [20]Yilmaz S,Aksoy E,Diken AI,et al.Dopamine administration is a risk factor for delirium in patients undergoing coronary artery bypass surgery[J].Heart Lung Circ,2016,25(5):493-498.
- [21]Kotermanski SE,Johnson JW,Thiels E.Comparison of behavioral effects of the NMDA receptor channel blockers memantine and ketamine in rats.[J].Pharmacol Biochem Behav,2013,109(8):67-76.
- [22]Schliebs R,Arendt T.The cholinergic system in aging and neuronal degeneration[J].Behav Brain Res,2011,221 (2):555-563.