成年期甲状腺功能减退对雄性小鼠海马神经颗粒素表达的影响

成年雄性昆明种小鼠分为对照组、丙基硫氧嘧啶(PTU)组、PTU+T4组,造模8周后,免疫组化和Western印迹法检测神经颗粒素(Ng)表达,发现甲状腺功能减退(甲减)小鼠海马区Ng表达降低,用T4治疗可使之恢复,提示海马内Ng减少可能是成年期甲减雄性小鼠认知功能受损的机制之一.     

围生期甲状腺功能减退仔鼠行为、学习和记忆研究

旷场试验、避暗试验、放射状八臂迷宫试验等结果显示，围生期甲状腺功能减退仔鼠情绪、空间学习记忆的改变与海马神经元凋亡增加相关。     

突触体素在甲状腺功能减退大鼠脑海马发育期的表达

探讨甲状腺激素对发育关键期大鼠海马各区突触体素表达的作用和影响,结果提示在脑发育关键期,甲状腺激素水平的减少改变了海马各区突触体索mRNA的表达和时相性,进而影响了该区域突触的发生及相关神经回路的建立。     

成年期甲状腺功能异常对患者空间记忆和物体记忆的影响

目的 探索成年期甲状腺功能异常对患者空间记忆和物体记忆的影响。方法 选择2013年3至11月在安徽医科大学第一附属医院内分泌科门诊就诊的甲状腺功能异常的患者,按甲状腺素水平将患者分为甲状腺功能亢进组（甲亢组,42例）和甲状腺功能减退组（甲减组,16例）,并按是否存在甲状腺相关抗体分为抗体阳性和抗体阴性亚组,收集患者背景资料,采用九盒迷宫实验检测空间记忆和物体记忆,以27例健康体检者为对照。采用SPSS 17.0进行统计学分析,组间差异比较采用t检验、单因素方差分析、秩和检验或χ2检验。结果 与对照组相比,甲亢患者的空间参考（z=2.407,P=0.016）和物体再认（z=7.553,P〈0.001）错误分值和甲减患者的物体再认（z=6.221,P〈0.001）错误分值显著增高;甲亢抗体阳性者的空间参考（z=3.695,P〈0.001）、空间工作（z=2.693,P=0.007）和物体再认（z=6.415,P〈0.001）及甲减抗体阳性者的空间工作（z=2.574,P=0.010）、物体再认（z=5.655,P〈0.001）错误分值显著增加,甲亢和甲减抗体阴性者的物体再认错误分值也显著增加（z=6.699、5.422,均P〈0.001）。结论 甲状腺功能障碍患者（尤其是甲状腺相关抗体阳性者）存在一定程度的认知功能损害,自身免疫因素可能参与其中。     

甲状腺素对甲状腺功能减退症大鼠海马syntaxin-1蛋白表达的影响

目的 研究成年期甲状腺功能减退症(简称甲减)大鼠海马突触前膜蛋白syntaxin-1的表达及不同剂量甲状腺素替代治疗的作用,探讨甲减脑损伤可能的分子机制.方法 健康3月龄成年SD雄性大鼠44只,体质量250 ～ 300 g,按体质量随机分为4组:甲减组、常规治疗组、大剂量治疗组和对照组,每组11只.甲减组、常规治疗组和大剂量治疗组每日腹腔注射丙基硫氧嘧啶(PTU) 10 mg/kg;4周后,甲减组继续给予PTU腹腔注射2周,常规治疗组和大剂量治疗组每日分别给予50、200μg/kg左旋甲状腺素腹腔注射2周;对照组每日腹腔注射等量生理盐水.造模结束后,采用放射免疫法检测4组大鼠血清T3、T4水平;采用免疫组化法检测4组大鼠海马syntaxin-1蛋白的表达.结果 与对照组[(0.65±0.05)、(55.20±3.56)nmol/L]比较,甲减组血清T3、T4[(0.34±0.04)、(43.01±2.95)nmol/L]明显降低(P均＜0.05),大剂量治疗组血清T3、T4[(1.11±0.10)、(96.68±6.42)nmol/L]显著升高(P均＜0.05);常规治疗组血清T3、T4[(0.63±0.05)、(55.04±3.77)nmol/L]与对照组比较,差异无统计学意义(P均＞0.05).甲减组大鼠海马CA1、CA3区起始层、放射层、腔隙层和齿状回(DG)分子层、多形层syntaxin-1蛋白表达水平(0.059±0.016、0.064±0.014、0.068±0.016,0.069±0.017、0.072±0.016、0.070±0.011,0.051±0.012、0.072±0.017)显著高于对照组(0.037±0.008、0.045±0.010、0.042±0.009,0.040±0.010、0.053±0.009、0.042±0.009,0.032±0.007、0.047±0.010,P均＜0.05);常规治疗组和大剂量治疗组各层syntaxin-1蛋白表达水平(0.041±0.011、0.046±0.017、0.044±0.014,0.037±0.008、0.051±0.010、0.043±0.010,0.033±0.011、0.045±0.014和0.040±0.010、0.045±0.011、0.043±0.010,0.033±0.009、0.050±0.010、0.041±0.009,0.032±0.009、0.046±0.009)较甲减组降低(P均＜ 0.05),与对照组比较,差异无统计学意义(P均＞0.05).结论 成年期甲减大鼠海马内syntaxin-1蛋白表达增加,常规剂量甲状腺素替代治疗能使其恢复至正常水平.     

甲状腺功能减退对慢性肝病的影响

正常生理状态下,肝脏在甲状腺激素的代谢、降解和排泄过程中发挥着重要作用。但当肝脏发生病变时,甲状腺功能减退现象明显增加,且多数患者无明显临床症状及体征。归纳了由于各种病因引起的慢性肝病及其不同发病阶段患者甲状腺功能水平的变化,发现甲状腺激素水平的下降对预测慢性肝病发生风险、病情判断及预后评估具有重要的指导价值。研究认为部分慢性肝病患者可通过甲状腺功能的调节,进而在一定程度上起到缓解病情、改善预后的治疗效果。此外,由于甲状腺代谢异常所引发的一系列基因失调或功能紊乱有可能成为部分慢性肝病新的治疗靶点,结论有待进一步研究证实。     

甲状腺激素对成年大鼠海马内突触结合蛋白Ⅰ表达的影响

目的 观察不同甲状腺激素水平对大鼠海马突触结合蛋白Ⅰ(syt Ⅰ)蛋白表达水平的影响.方法 复制雄性SD大鼠成年期甲状腺功能减退症(甲减)、甲状腺功能亢进症(甲亢)模型,用放射免疫法测定血清甲状腺激素T3、T4水平,用免疫组织化学超敏链霉菌抗生物素蛋白-过氧化物酶连结(S-P)法分析海马CA1区、CA3区和齿状回(DG)Syt Ⅰ蛋白的表达.结果 甲减组大鼠血清T3、T4水平[(0.34±0.12)、(41.03±11.37)nmol/L]明显低于对照组[(0.65±0.15)、(55.20±10.68)nmol/L,P<0.01或<0.05];甲减组Syt Ⅰ免疫反应产物阳性颗粒较对照组也明显减少,尤以海马CA1、CA3区锥体细胞层、放射层及DG区颗粒细胞层减少明显,Syt Ⅰ免疫反应产物,甲减组海马CA1区多形层(0.048±0.007)、细胞层(0.299±0.035)、放射层(0.042±0.007)、腔隙分子层(0.038±0.006)和CA3区的细胞层(0.085±0.019)、放射层(0.040±0.011)、腔隙分子层(0.038±0.006)及DG区颗粒细胞层(0.076±0.019)均较对照组(0.068±0.014、0.376±0.053、0.053±0.008、0.056±0.009,0.118±0.026、0.052±0.010、0.053±0.009、0.099±0.015)明显减少(P<0.01或<0.05).甲亢组大鼠血清T3、T4水平[(1.43±0.30)、(157.18±19.95)nmol/L]明显高于对照组(P<0.01).CA1区细胞层(0.322±0.050)、放射层(0.039±0.006)、腔隙分子层(0.042±0.006)和CA3区细胞层(0.098±0.034)、放射层(0.046±0.013)、腔隙分子层(0.046±0.010)及DG区颗粒层(0.085±0.024)、分子层(0.042±0.009)Syt Ⅰ免疫反应产物也较对照组减少(P<0.05或<0.01).结论 甲状腺激素水平增高或降低均可导致成年大鼠海马内SytⅠ蛋白表达减少.     

碘缺乏和碘过量对实验性甲状腺功能减退小鼠血脂代谢的影响

目的 观察碘缺乏和碘过量对实验性甲状腺功能减退(简称甲减)小鼠血脂代谢的影响,探讨碘不依赖于甲状腺激素的独立作用机制.方法 将雌性Balb/c小鼠按体质量随机分为6组:对照、重度低碘(SID)、轻度低碘(MID)、适碘(NI)、10倍碘过量(10HI)和50倍碘过量(50HI)组,每组10只.对照组饲以低碘饲料,其他各组饲以含0.2%甲基硫氧嘧啶的低碘饲料,同时饮用碘化钾(KI)配制的含碘量分别为326.79、0、196.08、326.79、3856.21、19 542.50 μg/L的去离子水.喂养3个月后,处死并收集小鼠外周血,分离血清.放射免疫分析法测定甲状腺激素水平,酶法检测血清中甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)水平.结果 ①SID[(21.27±9.63)μg/L]、MID[(23.41±3.93)μg/L]、NI[(22.57±4.66)μg/L]、10HI[(21.07±5.03)μg/L]和50HI组[(21.46±5.90)μg/L]血清TT4水平明显低于对照组[(42.15±8.26)μg/L,P均＜0.01],而各组间血清TT3水平比较,差异无统计学意义(F=0.99,P＞0.05).②10HI组TG水平[(1.17±0.16)mmol/L]与对照组[(1.39±0.22)mmol/L]和NI组[(1.51±0.22)mmol/L]比较,明显降低(P均＜0.05).50HI组TG和TC水平[(1.18±0.22)、(1.78±0.15)mmol/L]与对照组[(1.39±0.22)、(2.14±0.37)mmol/L]和NI组[(1.51±0.22)、(2.00±0.15)mmol/L]比较,明显降低(P均＜0.05).各组HDL-C、LDL-C水平比较,差异无统计学意义(F值分别为0.55、0.54,P均＞0.05).结论 碘可不依赖于甲状腺激素独立发挥调节甲减小鼠血脂的作用;监控碘的摄入量,对有效防治心血管疾病亦有重要作用.

Abstract：

Objective To observe the effects of iodine deficiency and iodine excess on the lipid metabolism in an experimental hypothyroid model of mice and to explore the roles of iodine independent of its role in thyroid hormones. Methods Female Balb/c mice were randomly divided into 6 groups: control, severe iodine deficiency (SID), mild iodine deficiency(MID), normal iodine (NI), 10-fold high iodine (10HI) and 50-fold high iodine(50HI), 10 in each group. The mice in control group were fed with low iodine forage, other mice were fed with low iodine forage containing 0.2% methylthiouracilum. All mice drank deionic water containing different concentrations of potassium iodide(KI). The iodine content in water was 326.79, 0, 196.08,326.79, 385621, 19 542.50 μg/L, respectively. After three months, thyroid hormones in the serum were determined by radioimmunoassay.Also, the blood samples were analyzed for total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesteiol (HDL-C) and low density lipoprotein cholesterol (LDL-C) and measured enzymatically by automatic analyzer. Results ①The levels of Tr4 in SID[(21.27 ± 9.63)μg/L], MID[(23.41 ± 3.93)μg/L], NI[(22.57 ±4.66)μg/L], 10HI [(21.07 ± 5.03) μg/L] and 50HI groups [(21.46 ± 5.90) μg/L] were distinctively decreased compared with control group[(42.15 ± 8.26)μg/L, all P ＜ 0.01]. There were no statistical significant differences of TT3 between different groups (F = 0.99, P > 0.05 ). ②The level of TG in 10HI group [ ( 1.17 ± 0.16)mmol/L ] was obviously decreased compared with control [(1.39 ± 0.22 )mmol/L] and NI groups[(151 ± 0.22)mmol/L, all P＜ 0.05].Both TG and TC in 50HI group[(1.18 ± 0.22), (1.78 ± 0.15)mmol/L] were significantly decreased compared with control [( 1.39 ± 0.22), (2.14 ± 0.37)mmol/L] and NI groups [(1.51 ± 0.22), (2.00 ± 0.15)mmol/L, all P ＜ 0.05].The difference of serum HDL-C and LDL-C between the groups was not significant(F = 0.55,0.54, all P ＞ 0.05 ).Conclusions Dietary iodine plays a role in the metabolism of serum lipids independent of thyroid hormones.Thus, monitoring the amount of iodine intake during sodium restriction should also be taken extremely important for effectively prevention and cure of cardiovascular disease.     

甲状腺功能减退对新生早期大鼠各脑区甲状腺激素受体mRNA表达的影响

目的探讨甲状腺功能减退（甲减）对新生早期大鼠各脑区甲状腺激素受体（TR）mRNA表达的影响。方法建立甲减Wistar大鼠动物模型，分别于仔鼠0、14、21、45d，用实时荧光定量PCR方法检测大脑、小脑、脑干和海马TR mRNA的表达。结果与对照组相比，各时间点甲减仔鼠各脑区TRα1 mRNA的表达量呈总体下调趋势，而甲减0d仔鼠大脑、小脑、脑干TRα2 mRNA表达量明显增高（t=8．18、6．23、3．68，P〈0．01），且45d仔鼠各脑区TRα2 mRNA表达量仍高于对照组（t大脑=5．50、t小脑=5．46、t脑干=4．10、t海马=11．83，P〈0．01），TRα1、TRα2 mRNA表达峰（21d）均延迟于对照组（14d）出现。甲减仔鼠TRβ1 mRNA表达变化趋势与对照组相一致，但45d仔鼠各脑区TRβ1 mRNA表达量均低于对照组（t大脑=4．64、t小脑=2．73、t脑干=3．90、t海马=5．07，P〈0．01或〈0．05）。结论甲减时甲状腺激素受体mRNA表达峰值的延迟出现以及异常的表达变化与克汀病脑损伤机制密切相关。     

原发性甲状腺功能减退与肾功能的关系

目的为探讨原发性甲状腺功能减退症（原发性甲减）患者甲状腺功能与肾功能的关系。方法检测31例原发性甲减患者和20例健康对照组的空腹血清游离三碘甲状腺原氨酸（FT3）、游离四碘甲状腺原氨酸（FT4）、高灵敏促甲状腺激素（sTSH）、尿素氮（BUN）、肌酐（Cr）、尿酸（UA）、肌酐清除率（CCr）、尿蛋白定性。结果原发性甲减患者Cr、UA、尿蛋白阳性率均明显高于对照组（P值均〈0．05），而CCr低于对照组（P〈0．05），并且FT3与CCr呈正相关（r=0．5441，P〈0．05），与UA呈负相关（r=-0．4372，P〈0．05）。但BUN在甲减组和对照组无统计学差异。结论提示原发性甲减患者常伴Cr、UA、尿蛋白阳性率升高，CCr下降。其FT3水平下降与CCr、UA升高关系更密切。     

Effect of episodic and working memory impairments on semantic and cognitive procedural learning at alcohol treatment entry

BACKGROUND: Chronic alcoholism is known to impair the functioning of episodic and working memory, which may consequently reduce the ability to learn complex novel information. Nevertheless, semantic and cognitive procedural learning have not been properly explored at alcohol treatment entry, despite its potential clinical relevance. The goal of the present study was therefore to determine whether alcoholic patients, immediately after the weaning phase, are cognitively able to acquire complex new knowledge, given their episodic and working memory deficits. METHODS: Twenty alcoholic inpatients with episodic memory and working memory deficits at alcohol treatment entry and a control group of 20 healthy subjects underwent a protocol of semantic acquisition and cognitive procedural learning. The semantic learning task consisted of the acquisition of 10 novel concepts, while subjects were administered the Tower of Toronto task to measure cognitive procedural learning. RESULTS: Analyses showed that although alcoholic subjects were able to acquire the category and features of the semantic concepts, albeit slowly, they presented impaired label learning. In the control group, executive functions and episodic memory predicted semantic learning in the first and second halves of the protocol, respectively. In addition to the cognitive processes involved in the learning strategies invoked by controls, alcoholic subjects seem to attempt to compensate for their impaired cognitive functions, invoking capacities of short-term passive storage. Regarding cognitive procedural learning, although the patients eventually achieved the same results as the controls, they failed to automate the procedure. Contrary to the control group, the alcoholic groups' learning performance was predicted by controlled cognitive functions throughout the protocol. CONCLUSION: At alcohol treatment entry, alcoholic patients with neuropsychological deficits have difficulty acquiring novel semantic and cognitive procedural knowledge. Compared with controls, they seem to use more costly learning strategies, which are nonetheless less efficient. These learning disabilities need to be considered when treatment requiring the acquisition of complex novel information is envisaged.     

突触前膜列阵蛋白1在成年期甲状腺功能减退症大鼠前额叶的表达

目的研究成年期甲状腺功能减退症(甲减)大鼠前额叶突触小体内突触前膜列阵蛋白1(syntaxin-1)的表达量及甲状腺素替代治疗后的恢复状况。方法用丙硫氧嘧啶建立成年期大鼠甲减模型共6 w,第5～6周分别给予5μg/100 g和20μg/100 g体重的左甲状腺素(左旋T4)腹腔注射,采用Western印迹方法分析甲减组、小剂量左旋T4替代治疗组、大剂量左旋T4替代治疗组及对照组大鼠前额叶syntaxin-1的表达情况。结果甲减组大鼠血清T3、T4水平低于对照组(P<0.05),前额叶内syntaxin-1的蛋白表达水平显著低于对照组(P<0.05);小剂量左旋T4替代治疗后,血清T3、T4恢复至正常水平,syntaxin-1蛋白的表达与对照组无明显差异(P>0.05);大剂量替代治疗后血清T3、T4高于正常,syntaxin-1蛋白表达的恢复更接近正常水平(P>0.05)。结论成年期甲减大鼠前额叶内syntaxin-1蛋白表达减少;左旋T4替代治疗能使其恢复,恢复的程度与治疗的剂量有关。     

NG-硝基精氨酸甲酯对慢性脑缺血大鼠记忆及诱导型一氧化氮合酶的影响

目的研究一氧化氮合酶抑制剂——NG-硝基-L-精氨酸甲酯（L—NAME）对慢性脑缺血大鼠学习空间记忆能力及海马区诱导型一氧化氮合酶（iNOS）表达的影响。方法3—4个月龄健康雄性Wistar大鼠54只,随机分为假手术组、模型组及L—NAME组,每组18只。采用双侧颈总动脉永久结扎法制备慢性脑缺血大鼠模型。L—NAME组在造模后第3周开始每日给予L—NAME（20mg·k-1·d-1配入每日饮用水中）。造模后2、4、6个月,利用Morris水迷宫方法检测各组大鼠学习空间记忆能力;观察海马区的组织病理学改变和iNOS的表达。结果①造模后2、4、6个月,模型组、L—NAME组的逃避潜伏期、搜索路径长度均比假手术组明显增多,差异有统计学意义（P〈0．01,P〈0．05）,L—NAME组比模型组明显缩短（P〈0．01,P〈0．05）。②HE染色显示,模型组和L．NAME组随着缺血时间的延长,海马区的锥体细胞损伤程度逐渐加重;L—NAME组各相应时间点损伤程度较模型组明显减轻。③模型组和L—NAME组海马CA1区iNOS阳性细胞数目随着缺血时间的延长而逐渐增多,均高于假手术组（P〈0．01,P〈0．05）;与模型组比较,L—NAME组的iNOS阳性细胞数目相对减少（P〈0．01,P〈0．05）。结论L—NAME可减轻慢性脑缺血所致的脑组织损伤,改善脑缺血所致的进行性学习空间记忆能力的下降;其可能的机制为通过抑制iNOS的表达而发挥神经保护作用。     

氟对大鼠胆碱酯酶活性和学习记忆功能的影响

目的 研究氟对慢性氟中毒大鼠学习、记忆功能的影响以及其可能的机制,探讨氟对脑组织胆碱酯酶活性的影响多氟中毒大鼠智力损伤程度的关系.方法 SD大鼠按性别和体质量随机分为3组,对照组:自由饮用自来水,含氟量低于1mg/L;低剂量染氟组:饮水含氟量为5mg/L;高剂量染氟组:饮水含氟量为50mg/L.实验3个月时检测大鼠行为学变化和脑组织胆碱酯酶活性.结果 高剂量染氟组大鼠的逃避潜伏期时间[(17.55±1.51)s]长于对照组[(12.07±0.97)s],两组比较差异有统计学意义(P＜0.05);高剂量染氟组探索实验目标次数[(2.88±0.35)次]与对照组[(4.00±0.50)次]比较,有降低趋势,但差异无统计学意义(P＞0.05);高剂量染氟组的乙酰胆碱酯酶和丁酰胆碱酯酶活性[(1.41±0.19)、(0.49±0.07)kU/g]均低于对照组[(1.88±0.13)、(1.04±0.16)kU/g)],差异均有统计学意义(P＜0.05).结论 过量氟在体内蓄积可使大鼠智力降低,脑内的胆碱酯酶活性降低可能是其机制之一.     

Verbal and visuospatial learning and memory function in children with moderate prenatal alcohol exposure

BACKGROUND: This study investigated the effects of moderate prenatal alcohol exposure on learning and memory in 14-year-old adolescents. The Children's Memory Scale was used to assess learning and memory function in the verbal/auditory and visual/spatial domains. In addition, both short- and long-term memory function were assessed. METHODS: Data were collected as part of the Maternal Health Practices and Child Development Project, a longitudinal study including 580 children and their mothers. Women were assessed during each trimester of pregnancy and with their children from birth to 16 years of age. At age 14, memory function was evaluated using the Children's Memory Scale, an assessment tool that measures learning and immediate and delayed memory function in the verbal and visual-spatial domains. RESULTS: Prenatal alcohol exposure during the first trimester predicted deficits in learning, short-term memory, and long-term memory, specifically in the verbal domain. Deficits in performance were specific to learning and memory of word-pairs. In addition, deficits in memory were mediated by learning performance. CONCLUSIONS: Results demonstrated that prenatal alcohol exposure lead to deficits in encoding processes as indicated by deficits in verbal learning. Initial deficits in acquisition were responsible for deficits in immediate and delayed recall of verbal information in children who were exposed to alcohol during pregnancy but did not have fetal alcohol syndrome.     

记忆增强肽对糖尿病小鼠学习,记忆功能及海马NT—3神经元的影响

目的 研究糖尿病小鼠学习、记忆功能及糖尿病小鼠脑海马内ＮＴ－３神经元表达变化,并观察记忆增强肽对糖尿病小鼠学习、记忆功能及脑海马内ＮＴ－３神经元表达的影响。方法 用链脲佐菌素（ｓｔｒｅｐｔｏｚｏｔｏｃｉｎ,ＳＴＺ）诱发糖尿病小鼠模型,并皮下注射记忆增强肽,４周后行水迷宫试验。水迷宫试验后对小鼠进行灌注固定,邓小鼠脑海马进行冰冻切片行免疫组化染色。结果 １记忆增强肽不影响糖尿病小鼠的血糖水平;２行为