本文選題：甲狀腺功能減退癥　切入點(diǎn)：甲狀腺功能亢進(jìn)癥　出處：《云南大學(xué)》2015年博士論文　論文類型：學(xué)位論文

【摘要】：本文包括兩部分內(nèi)容：第一部分,甲減和甲亢雙向作用于SD大鼠的抑郁和焦慮樣行為；第二部分,SD大鼠海馬內(nèi)高甲狀腺素?fù)p傷背景恐懼記憶的鞏固。 第一部分：甲狀腺素異常經(jīng)常與抑郁癥相關(guān),長期以來這方面已受到關(guān)注,但它們間的具體因果關(guān)系一直保持著爭議。為了說明甲狀腺功能(甲功)異常與抑郁癥之間的因果關(guān)系,我們用給SD大鼠灌胄(I.G)1引碘(131I)以造模甲狀腺功能減退癥(甲減)大鼠,給SD大鼠腹腔注射(I.P.)注射左旋甲狀腺素(LT4)以造模甲狀腺功能亢進(jìn)癥(甲亢)大鼠。單次給SD大鼠胃內(nèi)注入(I.G.)131I(5mCi/kg body weight),9天后其血清游離四碘甲狀腺原氨酸(FT4)和游離三碘甲狀腺原氨酸(FT3)將長期低于正常水平。這些大鼠在強(qiáng)迫游泳(FST)和糖水偏愛實(shí)驗(yàn)中,表現(xiàn)為降低的抑郁樣行為,在高架十字迷宮(EPM)中表現(xiàn)為抗焦慮樣行為。和對照組大鼠(胃內(nèi)灌相同體積的生理鹽水NS)相比,甲減大鼠大腦內(nèi)的五羥色胺(5-HT)水平顯著降低,但海馬內(nèi)的腦源性神經(jīng)營養(yǎng)因子(BDNF)表達(dá)水平顯著升高。在甲減大鼠腹腔內(nèi)注入LT4將逆轉(zhuǎn)降低的血清甲狀腺素,并逆轉(zhuǎn)其抗抑郁樣行為。相反,在大鼠腹腔內(nèi)每周注射LT4(15μg/kg body weight),將導(dǎo)致大鼠血清的FT4和FT3比對照組大鼠(腹腔內(nèi)注入相同體積的NS)高出10多倍。甲亢大鼠在FST中表現(xiàn)為抑郁樣行為,在EPM中表現(xiàn)為焦慮樣行為,比對照組在大腦內(nèi)有更高的5-HT,在海馬內(nèi)有顯著降低的BDNF表達(dá)。用抗抑郁藥丙咪嗪(15mg/kg)注入甲亢大鼠腹腔,將顯著降低血清的FT4,也隨之降低其抑郁和焦慮樣行為,但相對于對照組和甲減組大鼠,其導(dǎo)致腦內(nèi)的5.HT進(jìn)一步升高�？傊�,我們的結(jié)果提示了甲減和甲亢將雙向調(diào)節(jié)大鼠的焦慮和抑郁樣行為,可能是通過調(diào)節(jié)海馬內(nèi)的BDNF水平起作用的。這些數(shù)據(jù)為今后更深入的臨床研究打下了基礎(chǔ)。 第二部分：甲狀腺素在大腦許多正常功能中起著關(guān)鍵作用,其中包括認(rèn)知功能。本研究主要用背景條件性恐懼記憶研究四碘甲狀腺原氨酸(T4)在情緒學(xué)習(xí)和記憶中的作用。在背景條件性恐懼記憶訓(xùn)練前24小時(shí)和訓(xùn)練后立即、2小時(shí)后、23.5小時(shí)時(shí)等四個(gè)時(shí)間點(diǎn),分別在不同雄性SD大鼠的背側(cè)海馬(DH)內(nèi)微量注入左旋甲狀腺素(LT4,0.4μg/μl×1ul/lateral×2laterals, LT4-注射組)或生理鹽水NS (vehicle,1μl/lateral×2laterals對照組)。在訓(xùn)練時(shí)(DO)、訓(xùn)練后24小時(shí)(D1)、7天(D7)、14天(D14),在相同的恐懼性記憶訓(xùn)練箱中分別記錄大鼠不動(dòng)時(shí)間占每次實(shí)驗(yàn)觀察時(shí)間的百分比,以此作為反映大鼠對厭惡刺激的記憶強(qiáng)度。在恐懼性記憶訓(xùn)練箱中,厭惡刺激為電刺激(0.8mA×2Seconds/time×5times)大鼠足部。DH內(nèi)(I.H.)注入LT4后的3天內(nèi),海馬內(nèi)的游離四碘甲狀腺原氨酸(FT4)顯著高于對照組,但海馬內(nèi)的游離三三碘甲狀腺原氨酸(FT3)以及前額葉(PFC)和血液中的FT4和FT3均不高于對照組。在連續(xù)6個(gè)試驗(yàn),每個(gè)試驗(yàn)2分鐘,共12分鐘的背景條件性恐懼記憶訓(xùn)練中,訓(xùn)練前24小時(shí)DH內(nèi)LT4-注射組的不動(dòng)時(shí)間百分比與對照組比較無顯著差異,提示學(xué)習(xí)能力并未顯著受損。在背景條件性恐懼記憶訓(xùn)練后D1、D7、D14共三天,每天5分鐘的背景條件恐懼記憶提取中,訓(xùn)練后立即或2小時(shí)后于DH內(nèi)LT4-注射組的不動(dòng)時(shí)間百分比比對照組顯著減少,提示長期記憶(LTM)顯著受損；但訓(xùn)練后23.5小時(shí)LT4.注射組的不動(dòng)時(shí)間百分比與對照組比較在訓(xùn)練后上述3天均無顯著差異,提示LTM未顯著受損。訓(xùn)練后立即或2小時(shí)后于DH內(nèi)LT4-注射組受損的LTM類似于條件性恐懼記憶訓(xùn)練后立即腹腔內(nèi)注入(I.P.) LT4(15μg/kg)后在D1、D7、D14的LTM顯著受損。腹腔內(nèi)注入LT4后的2小時(shí)時(shí)海馬內(nèi)的FT4而不是FT3顯著升高,24小時(shí)時(shí)海馬內(nèi)的腦源性神經(jīng)營養(yǎng)因子(BDNF)顯著降低。以上結(jié)果提示海馬內(nèi)高T4顯著損傷背景條件性恐懼記憶是有時(shí)間限制的,其機(jī)制至少是通過顯著降低海馬內(nèi)BDNF來實(shí)現(xiàn)的。本研究首次揭示海馬內(nèi)注入LT4僅顯著損傷雄性SD大鼠背景條件性恐懼記憶的鞏固期,而不顯著損傷學(xué)習(xí)期和記憶提取。這為今后有針對性地研究和更好地選擇治療甲亢記憶受損的治療方案提供了參考。
[Abstract]:This paper includes two parts: the first part is hypothyroidism and hyperthyroidism on the two-way action of depression and anxiety like behavior in SD rats; the second part is the consolidation of background fear memory of hyperthyroxine in SD rats.
The first part: the thyroid abnormalities often associated with depression, a long time it has been paid attention, but the specific causal relationship between them has remained controversial. In order to illustrate the thyroid function (a function) the causal relationship between abnormal and depression, we use Guan Zhou to SD rats (I.G) 1 (131I) of iodine die hypothyroidism (hypothyroidism) rats, SD rats by intraperitoneal injection (I.P.) injection of levothyroxine (LT4) in the model of hyperthyroidism (hyperthyroidism) rats. Single injection to SD rat stomach (I.G.) 131I (5mCi/ kg body weight), four thyroid ammonia after 9 days of free acid (FT4) and serum free triiodothyronine three (FT3) will be lower than the normal level. The rats in forced swimming (FST) and sucrose preference test, performance for depression like behavior to reduce, in the elevated plus maze (EPM) is in the form of anti anxiety like behavior. And the rats in the control group (normal saline NS gastric irrigation of the same volume) compared to hypothyroid rats in the brains of five hydroxytryptamine (5-HT) levels were significantly reduced, but the brain derived neurotrophic factor in the hippocampus (BDNF) expression level was significantly increased in hypothyroidism rats. Intraperitoneal injection of LT4 in the inverse transfer of serum thyroxine reduce, and reverse the anti depressive like behavior. On the contrary, in rats after intraperitoneal injection of LT4 per week (15 g/kg body weight), will result in the serum of rats FT4 and FT3 rats than in the control group (intraperitoneal injection of the same volume of NS) of more than 10 times higher. Hyperthyroid rats in FST performance as the depression like behavior in EPM showed anxiety like behavior than the control group, with higher 5-HT in the brain, have reduced the expression of BDNF in hippocampus. With antidepressant imipramine (15mg/kg) intraperitoneal injection of hyperthyroid rats, significantly reduced serum FT4, with reducing the depression and anxiety like But, compared with the control group and hypothyroidism group rats, resulting in brain 5.HT increased further. In conclusion, our results suggest that the hypothyroid and hyperthyroid rats will regulate anxiety and depression like behavior, it may regulate the level of BDNF in the hippocampus plays a role. These data for future clinical research deep foundation.
The second part: thyroid hormone plays a key role in many normal brain functions, including cognitive function. This research mainly used the research background of conditioned fear memory four triiodothyronine (T4) in emotional learning and memory function. In the background of conditioned fear memory training 24 hours before and immediately after training, after 2 hours 23.5 hours, four time points respectively in the dorsal hippocampus of different male SD rats (DH) microinjection of levothyroxine (LT4,0.4 g/ L * 1ul/lateral * 2laterals, LT4- injection group) or saline (NS vehicle, 1 l/lateral * 2laterals control group. (in training) DO), 24 hours after the training (D1), 7 days (D7), 14 days (D14), in fear of the same memory training box in the immobility time of the rats were recorded for each experiment to observe the percentage of time, so as to reflect on rat memory strength aversive stimuli. In Fear memory training box, aversive stimuli into electrical stimulation (0.8mA * 2Seconds/time * 5times) rat foot.DH (I.H.) LT4 within 3 days after the injection, four free triiodothyronine (FT4) in the hippocampus was significantly higher than the control group, but 33 free triiodothyronine in hippocampus (FT3) and the prefrontal cortex (PFC) and FT4 in blood and FT3 were not significantly higher than the control group. In 6 consecutive tests, each test 2 minutes, 12 minutes of conditioned fear memory training, training 24 hours before DH in LT4- injection group, the immobility time and the percentage of the control group showed no significant difference that suggests that learning ability does not significantly damaged. In the background of conditioned fear memory after training, D1, D7, D14 a total of three days, every 5 minutes of background extraction of fear memory, immediately after training or 2 hours after LT4- injection in DH group significantly decreased the immobility time percentage than the control group. In the long-term memory (LTM) significantly impaired; but the training 23.5 hours after LT4. injection group of real time compared with the control group in the 3 day after the training had no significant difference, suggesting that LTM was not significantly impaired. Immediately after training or after 2 hours in the DH group were injected with LT4- damaged LTM similar to the conditioned fear memory immediately after training injection intraperitoneal (I.P.) LT4 (15 g/kg) in D1, D7, D14, LTM were significantly damaged. Intraperitoneal injection 2 hours after LT4 FT4 in the hippocampus is not FT3 significantly increased at 24 h in the hippocampus brain derived neurotrophic factor (BDNF) decreased significantly. These results suggest that hippocampal T4 damage significantly high background of conditioned fear memory is a time limit, the mechanism is at least through significantly decreased in hippocampus of BDNF. This is the first study to show hippocampal injection of LT4 in the only significant damage in male SD rats background of conditioned fear memory Consolidation period does not significantly damage learning period and memory retrieval. This provides a reference for targeted research and better choice of treatment regimens for hyperthyroidism memory impairment.

【學(xué)位授予單位】：云南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R749

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