本文選題：抑郁癥 + 下丘腦�。� 參考：《浙江大學(xué)》2016年博士論文

【摘要】：第一部分抑郁癥患者下丘腦視交叉上核GABA改變的研究背景：抑郁癥又稱情感障礙,主要包括重型抑郁障礙(major depressive disorder, MDD)和雙相情感障礙(bipolar disorder, BD)。抑郁癥的主要發(fā)病機(jī)制包括過度激活的應(yīng)激反應(yīng)調(diào)節(jié)系統(tǒng),即下丘腦-垂體-腎上腺(hypothalamo-pituitary-adrenal, HPA)軸。抑郁癥的另一主要病理特征是生物鐘也即下丘腦視交叉上核(suprachiasmatic nucleus, SCN)功能紊亂,導(dǎo)致睡眠一覺醒節(jié)律紊亂以及進(jìn)食障礙等癥狀。血管加壓素(arginine vasopressin, AVP)是SCN合成的主要神經(jīng)肽之一。在人類和動(dòng)物下丘腦都觀察到SCN神經(jīng)元有向下丘腦室旁核(paraventricular nucleus, PVN)的直接或間接神經(jīng)投射,提示SCN與PVN之間具有相互調(diào)節(jié)作用。此外,這兩個(gè)核團(tuán)均受到來自下丘腦其他部位例如下丘腦食欲素(orexin)系統(tǒng)的神經(jīng)支配,提示下丘腦內(nèi)由神經(jīng)遞質(zhì)和神經(jīng)調(diào)質(zhì)所介導(dǎo)的神經(jīng)環(huán)路功能障礙。值得注意的是,盡管SCN神經(jīng)元幾乎均為γ-氨基丁酸(Gamma amino butyric acid, GABA)能神經(jīng)元,迄今為止抑郁癥患者SCN內(nèi)GABA變化尚未獲得研究,它們與下丘腦orexin及其和PVN活性改變之間的關(guān)聯(lián)也尚未被研究。因此,本研究旨在闡明抑郁癥患者下丘腦SCN中GABA能變化及其和SCN內(nèi)神經(jīng)肽即AVP、下丘腦orexin變化之間的關(guān)聯(lián)。方法：在13位抑郁癥患者(6位MDD,7位BD)和13位按照性別、年齡、死亡時(shí)間、組織固定和貯存時(shí)間等參數(shù)良好匹配的對照組的下丘腦SCN中,采用免疫細(xì)胞化學(xué)法(immunocytochemistry, ICC)測定SCN內(nèi)GABA能合成關(guān)鍵酶,即谷氨酸脫羧酶(glutamic acid decarboxylase, GAD)65/67-免疫反應(yīng)性(immunoreactivity, ir)和AVP-ir;采用原位雜交技術(shù)(in situ hybridization, ISH)測定SCN內(nèi)GAD67-mRNA水平,采用圖像分析方法(image analysis)定量研究上述參數(shù)。對SCN數(shù)據(jù)和我們先前研究的相同個(gè)體的下丘腦orexin-ir表達(dá)水平做相關(guān)分析。結(jié)果：AVP-ir神經(jīng)元和神經(jīng)纖維廣泛分布于下丘腦SCN, PVN、視上核(supraoptic nucleus, SON)以及位于PVN和SON之間的附加核(accessory nuclei). GAD65/67-ir神經(jīng)纖維密集分布于丘腦、下丘各核團(tuán)包括SCN、PVN、SON等。GAD67-mRNA-ISH信號也分布于丘腦以及下丘腦的SCN, PVN、SON等核團(tuán)。抑郁癥患者SCN內(nèi)GAD65/67-ir較對照組顯著上升約54%(P= 0.044), GAD67-mRNA較對照組顯著上升165%(P=0.029)。此外,抑郁癥女性患者SCN內(nèi)AVP-ir較女性對照顯著相升高155%(P=0.008),而抑郁癥男性SCN內(nèi)中AVP-ir和男性對照相比沒有顯著差異。在對照組,SCN-AVP-ir和年齡呈顯著負(fù)相關(guān)(Rho=-0.745, P=0.003),男性抑郁癥組也觀察到SCN-AVP-ir和年齡之間的顯著負(fù)相關(guān)(Rho=-0.766, P= 0.027),而女性抑郁癥組內(nèi)這種相關(guān)性消失。此外,在男性對照組下丘腦orexin-ir和SCN內(nèi)GAD65/67-ir呈顯著正相關(guān)(Rho= 0.790, P= 0.020),女性對照組內(nèi)則無此相關(guān)性。上述所有參數(shù)在MDD和BD患者之間相比無顯著差異。結(jié)論：抑郁癥患者SCN內(nèi)GABA顯著升高(表現(xiàn)為GAD65/67-ir和GAD67-mRNA均顯著升高)可能在SCN功能紊亂中扮演重要角色；SCN內(nèi)AVP-ir以及下丘腦orexin-ir的性別相關(guān)性異常表達(dá)也和抑郁癥中的生物學(xué)節(jié)律紊亂及HPA軸活性改變的性別差異密切相關(guān)。第二部分Sprague-Dawley大鼠應(yīng)激反應(yīng)中的性別差異：下丘腦和外周激素改變背景：已有研究表明,性別差異在抑郁癥中扮演著重要角色,過度激活的應(yīng)激反應(yīng)是抑郁癥的重要發(fā)病機(jī)制。應(yīng)激反應(yīng)調(diào)節(jié)系統(tǒng)下丘腦—垂體-腎上腺(hypothalamo-pituitary-adrenal, HPA)軸在抑郁癥中活性異常,下丘腦促腎上腺皮質(zhì)激素釋放素(corticotropin-releasing hormone, CRH)過度激活。而個(gè)體的過度應(yīng)激也可以導(dǎo)致抑郁癥發(fā)生和/或加劇。我們組和其他研究組的先前研究發(fā)現(xiàn),性激素例如雌二醇(estradiol, E2),睪酮(testosterone, T)可以通過其相應(yīng)受體即雌激素受體α或者β(estrogen receptor α, β; ERa, ERβ)、雄激素受體(androgen receptor, AR)而作用于CRH基因啟動(dòng)子調(diào)節(jié)CRH基因表達(dá),進(jìn)而調(diào)節(jié)HPA軸活性。雌激素促進(jìn)CRH基因表達(dá)而雄激素抑制該過程,這種機(jī)制可能是應(yīng)激反應(yīng)中的性別差異以及抑郁癥發(fā)病性別差異的基礎(chǔ)。為了進(jìn)一步利用應(yīng)激動(dòng)物模型進(jìn)行抑郁癥相關(guān)研究,我們探索了大鼠急、慢性應(yīng)激反應(yīng)中的性別差異,測定血漿皮質(zhì)酮(corticosterone, CORT)以及性激素(T和E2)水平；測定下丘腦應(yīng)激相關(guān)分子包括ERα、ERβ、AR、芳香化酶(aromatase, ARO)—將雄激素轉(zhuǎn)化為雌激素的關(guān)鍵酶、CORT受體包括鹽皮質(zhì)激素受體(mineralcorticoid receptor,MR)、糖皮質(zhì)激素受體(glucocorticoid receptor, GR),以及神經(jīng)肽CRH、血管加壓素(arginine vasopressin, AVP)和催產(chǎn)素(oxytocin, OXT)的mRNA表達(dá)改變。方法：雌性Sprague-Dawley (SD)大鼠隨機(jī)分組：將慢性不可預(yù)知性溫和應(yīng)激(chronic unpredicted mild stress, CUMS)組、急性足底電擊(foot shock, FS)組以及對照組三組再細(xì)分為動(dòng)情前期、動(dòng)情間期犧牲組(共6組)。雄性SD大鼠隨機(jī)分為組：CUMS組、FS組以及對照組(共3組)。CUMS組大鼠在三周應(yīng)激以后與對照組進(jìn)行行為學(xué)測定,包括曠場實(shí)驗(yàn)、糖水偏好實(shí)驗(yàn)。犧牲各組大鼠留取軀干血、下丘腦等樣本。采用酶聯(lián)免疫吸附法測定血漿CORT,放射性免疫法測定血漿T和E2,采用實(shí)時(shí)定量PCR (Quantitative reverse transcription PCR, Q-PCR)法測定下丘腦應(yīng)激相關(guān)分子ERα、ERβ、AR、ARO、MR、GR、CRH、AVP和OXT的mRNA表達(dá)水平。結(jié)果：CUMS導(dǎo)致雌鼠的性周期紊亂,表現(xiàn)為動(dòng)情間期延長。相比于雄鼠,雌鼠在行為學(xué)測試中顯示更多的焦慮、抑郁樣行為；雌性CUMS鼠比雄性CUMS鼠具有更多的下丘腦應(yīng)激相關(guān)分子顯著改變包括CRH-mRNA顯著升高(P=0.05),MR-mRNA和GR-mRNA顯著減低(P=0.003,P=0.001)等；而雄鼠CUMS組AVP-mRNA顯著高于雄性對照組(P0.001)。CUMS、FS雌鼠血漿CORT相對于基礎(chǔ)水升高的幅度顯著大于雄鼠(雌鼠,CUMS組為對照組水平的18.7倍,FS組34.3倍；雄鼠,CUMS組1.8倍,FS組3.6倍)。CUMS和FS應(yīng)激后,雌鼠血漿E2和T水平顯著降低(P ≤0.039),而FS雄性大鼠的E2水平有升高趨勢(P=0.056), CUMS雄性大鼠的血漿T水平顯著降低(P=0.0047)。結(jié)論：急性或慢性應(yīng)激導(dǎo)致SD大鼠在行為學(xué)、血漿激素以及下丘腦應(yīng)激相關(guān)分子表達(dá)等方面表現(xiàn)出明顯性別差異性變化,和人類應(yīng)激反應(yīng)、抑郁癥中性別差異改變之間存在許多符合處。第三部分戊巴比妥鈉或異氟烷麻醉對大鼠應(yīng)激反應(yīng)研究結(jié)果的影響背景：應(yīng)激反應(yīng)紊亂與抑郁癥發(fā)病之間的關(guān)聯(lián)促進(jìn)了人們對應(yīng)激動(dòng)物模型的研究。調(diào)節(jié)應(yīng)激反應(yīng)的關(guān)鍵系統(tǒng)下丘腦—垂體—腎上腺(hypothalamo-pituitary-adrenal, HPA)軸在抑郁癥中過度激活。研究發(fā)現(xiàn),性激素例如睪酮(testosterone,T)和雌二醇(estradiol, E2)以及神經(jīng)肽例如促腎上腺皮質(zhì)激素釋放素(corticotropin-releasing hormone, CRH),精氨酸血管加壓素(arginine vasopressin, AVP)和催產(chǎn)素(oxytocin, OXT)等都在應(yīng)激反應(yīng)調(diào)節(jié)中起重要作用。值得注意的是,在應(yīng)激反應(yīng)的研究中,犧牲動(dòng)物前使用麻醉劑是常用的試驗(yàn)方法,然而麻醉劑對應(yīng)激反應(yīng)研究結(jié)果的影響尚未獲得明確結(jié)論。有報(bào)道麻醉劑可以通過抑制腦內(nèi)興奮性受體例如天冬氨酸(N-Methyl-D-Aspartate, NMDA)受體亞型NR2B、神經(jīng)元型煙堿樣乙酰膽堿受體(neuronal-type nicotinic acetylcholine receptor, nnAChR),以及激活腦內(nèi)抑制性受體例如γ-氨基丁酸(Gamma amino butyric acid, GABA) A受體(GABAA receptor, GABAAR)而影響腦功能。迄今為止,常用的犧牲實(shí)驗(yàn)動(dòng)物前所采用的麻醉方法,例如腹腔注射戊巴比妥鈉麻醉、異氟烷氣體吸入麻醉等是否影響急性應(yīng)激性反應(yīng)研究中所獲得的參數(shù)結(jié)果尚屬未知。本文旨在研究不同的犧牲動(dòng)物的方式,即直接斷頭犧牲、腹腔注射戊巴比妥鈉后斷頭犧牲、異氟烷吸入麻醉后斷頭犧牲對急性應(yīng)激反應(yīng)研究結(jié)果的影響,包括對血漿應(yīng)激激素皮質(zhì)酮(corticosterone, CORT)、血漿性激素T和E2激素水平的影響,以及對下丘腦應(yīng)激相關(guān)分子如CRH、AVP、OXT的mRNA表達(dá),以及額葉應(yīng)激相關(guān)分子如NR2B、nnAChR、GABAAR的mRNA表達(dá)的影響。方法：雄性Sprague-Dawley (SD)大鼠隨機(jī)分為足底電擊(foot shock, FS)組和對照組,并根據(jù)犧牲大鼠的方法進(jìn)一步分亞組：直接斷頭犧牲組、腹腔注射戊巴比妥鈉后斷頭犧牲組、異氟烷吸入麻醉后斷頭犧牲組(共6組)。此外還設(shè)立非應(yīng)激對照的腹腔注射生理鹽水后斷頭犧牲組。留取軀干血、下丘腦和額葉標(biāo)本。采用酶聯(lián)免疫吸附法測定血漿CORT,放射性免疫法測定血漿T,酶免疫法測定血漿E2,實(shí)時(shí)定量PCR (Quantitative reverse transcription PCR, Q-PCR)法測定下丘腦應(yīng)激相關(guān)分子CRH、AVP和OXT以及前額葉應(yīng)激相關(guān)分子NR2B,GABAAR和nnAChR-mRNA表達(dá)的改變。結(jié)果：在直接斷頭犧牲組和異氟烷吸入后犧牲組,FS顯著升高了血漿CORT水平(P0.001),而在戊巴比妥鈉腹腔注射犧牲組,未觀察到FS對血漿CORT水平的顯著影響(P=0.132)。在對照組中,腹腔注射生理鹽水或者腹腔注射戊巴比妥鈉都顯著升高了血漿CORT的水平(P=0.008,P=0.004)。性激素和腦內(nèi)應(yīng)激相關(guān)分子的mRNA水平在各組之間均無無顯著性差異(P≥0.132)。結(jié)論：腹腔注射,而非麻醉藥物本身,導(dǎo)致了動(dòng)物的額外應(yīng)激。這種額外應(yīng)激導(dǎo)致血漿CORT水平升高,使得原本由急性FS應(yīng)激所導(dǎo)致的血漿CORT水平在應(yīng)激組和對照組之間的顯著差異“消失”,因而干擾了研究結(jié)果。這類麻醉方法并未對血漿性激素或者腦中應(yīng)激相關(guān)分子mRNA的表達(dá)造成顯著影響。異氟烷氣體吸入麻醉對急性應(yīng)激反應(yīng)無顯著影響。從動(dòng)物倫理學(xué)角度考慮,異氟烷氣體吸入麻醉后犧牲是一項(xiàng)較優(yōu)的實(shí)驗(yàn)方法。
[Abstract]:The study background of GABA changes in the hypothalamic suprachiasmatic nucleus in the first part of depression: depression is also called affective disorder, mainly including heavy depressive disorder (major depressive disorder, MDD) and bipolar affective disorder (bipolar disorder, BD). The main pathogenesis of depression includes the overly activated stress response regulation system, that is, the hypothalamus. The brain - pituitary - adrenal (hypothalamo-pituitary-adrenal, HPA) axis. Another major pathological feature of depression is the dysfunction of the suprachiasmatic nucleus (SCN) in the hypothalamus, which leads to the symptoms of sleep disorder and eating disorders. The vasopressin (arginine vasopressin, AVP) is a SCN synthesis. One of the major neuropeptides. In both human and animal hypothalamus, SCN neurons have direct or indirect nerve projections to the paraventricular paraventricular nucleus (paraventricular nucleus, PVN), suggesting the interaction between SCN and PVN. In addition, these two nuclei are derived from other parts of the hypothalamus, such as the hypothalamus orexin (orexin) system. It is worth noting that although SCN neurons are almost all Gamma amino butyric acid (GABA) neurons, the changes in SCN GABA in the patients with depression so far have not been studied, and they are with the hypothalamus orexin. The association between PVN activity and its activity has not been studied. Therefore, this study aims to elucidate the correlation between the changes in the GABA energy in the hypothalamus SCN and the changes in the SCN neuropeptide, AVP, and the hypothalamus orexin. Methods: in 13 depressive patients (6 MDD, 7 BD) and 13 according to sex, age, death time, and tissue fixation In the hypothalamic SCN of the control group with good matching of storage time and other parameters, immunocytochemistry (ICC) was used to determine the key enzyme of GABA in SCN, that is, glutamic acid decarboxylase, GAD 65/67- immunoreactivity (immunoreactivity, IR). Ridization, ISH) measured the level of GAD67-mRNA within SCN, using the image analysis method (image analysis) to quantify the above parameters. The correlation analysis of the SCN data and the level of the hypothalamic orexin-ir expression in the same individuals we previously studied. Results: AVP-ir neurons and nerve fibers were widely distributed in the hypothalamus SCN, PVN, supra nuclear (supraoptic). Nucleus, SON) and the additional nucleus (accessory nuclei) between PVN and SON. The GAD65/67-ir nerve fibers are densely distributed in the thalamus, and the nuclei of the lower colliculus, including SCN, PVN, SON, etc., are also distributed in the thalamus and the hypothalamus. .044), GAD67-mRNA was significantly higher than that of the control group (P=0.029). In addition, the SCN AVP-ir in SCN was significantly higher in women with depression than in the female control (P=0.008), while there was no significant difference between AVP-ir and men in the SCN of depression men. In the control group, there was a significant negative correlation between SCN-AVP-ir and age (Rho=-0.745, P=0.003) and male depression in the control group. The group also observed a significant negative correlation between SCN-AVP-ir and age (Rho=-0.766, P= 0.027), but this correlation disappeared in the female depression group. In addition, there was a significant positive correlation between the orexin-ir and SCN in the hypothalamus orexin-ir and SCN in the male control group (Rho= 0.790, P= 0.020), and there was no such correlation in the female control group. All the parameters were in MDD and BD. There is no significant difference between patients. Conclusion: the significant increase in SCN GABA in the patients with depression (showing a significant increase in GAD65/67-ir and GAD67-mRNA) may play an important role in SCN dysfunction; the abnormal expression of AVP-ir in SCN and the sex correlation of orexin-ir in the hypothalamus is also associated with the biological rhythm disorder and HPA axis in the depression. Gender differences in sexual changes are closely related. Second the gender differences in the stress response in the second part of the rats: the changes in the hypothalamus and peripheral hormones: Previous studies have shown that gender differences play an important role in depression, and excessive activation of stress response is an important pathogenesis of depression. The hypothalamic - pituitary - adrenal (hypothalamo-pituitary-adrenal, HPA) axis is abnormally active in depression, and the hypothalamic corticotropin releasing hormone (corticotropin-releasing hormone, CRH) is excessively activated. And individual overstress can also lead to depression and / or aggravation. Our group and other research groups have previously studied Now, sex hormones such as estradiol, E2, and testosterone (testosterone, T) can be used to regulate the gene expression by the receptor (estrogen receptor alpha, beta, ERa, ER beta), androgen receptor (androgen receptor, AR) by its corresponding receptors, and then regulate the activity of the axis. This mechanism may be the basis of gender differences in stress responses and gender differences in depression. In order to further use stress animal models to study depression related studies, we explored the sexual differences in acute and chronic stress responses in rats, and the determination of plasma corticosterone (corticosterone, CORT). ) and the levels of sex hormones (T and E2); the determination of hypothalamic stress related molecules including ER alpha, ER beta, AR, and aromatase (aromatase, ARO) - the key enzymes that convert androgens into estrogen, CORT receptors including the corticosteroid receptor (mineralcorticoid receptor, MR), glucocorticoid receptors, and neuropeptides, MRNA expression changes of arginine vasopressin (AVP) and oxytocin (oxytocin, OXT). Methods: female Sprague-Dawley (SD) rats were randomly divided into three groups: chronic unpredictable mild stress (chronic unpredicted mild stress) group, acute foot shock group, and control group, and then divided into estrus. The male SD rats were randomly divided into groups: group CUMS, group FS and control group (3 groups), after three weeks of stress, the male rats were randomly divided into groups, including the open field experiment and the sugar water preference experiment. The rats left the trunk blood, the hypothalamus and other samples were sacrificed by the enzyme linked immunosorbent assay. The plasma T and E2 were determined by radioimmunoassay, and the expression level of the hypothalamic stress related molecules ER a was measured by real-time quantitative PCR (Quantitative reverse transcription PCR, Q-PCR). Results: the sexual cycle disorder of the female rats was caused by the prolongation of the interval of estrus. Compared with the male rats, it was compared with the male rat. The female mice showed more anxiety and depressive behavior during the behavioral test, and the significant changes in the hypothalamic stress related molecules in female CUMS mice were significantly higher than that of the male CUMS rats (P=0.05), MR-mRNA and GR-mRNA significantly decreased (P=0.003, P=0.001), while the AVP-mRNA of male rats in group CUMS was significantly higher than that of the male control group (P0.001).C. UMS, the increase of plasma CORT in FS female rats was significantly greater than that of the male rats (female rats, 18.7 times the level of the control group in the CUMS group, 34.3 times in the FS group, 1.8 times in the male, the CUMS group and 3.6 times in the FS group), and the level of E2 and T in the female rats decreased significantly after the.CUMS and FS stress (P < 0.039). The level of plasma T in rats was significantly decreased (P=0.0047). Conclusion: acute or chronic stress results in obvious gender differences in behavior, plasma hormone and hypothalamic stress related molecules expression in SD rats, and human stress response. There are many conforms between the changes of gender differences in depression. Third partial glutba is found. The influence of sodium or isoflurane on the results of stress response study in rats: the association between stress disorder and depression promotes the study of stress animal models. The hypothalamus pituitary adrenal (hypothalamo-pituitary-adrenal, HPA) axis, the key system regulating stress response, excesses depression The study found that sex hormones such as testosterone (T) and estradiol (estradiol, E2) as well as neuropeptides such as corticotropin-releasing hormone (CRH), arginine vasopressin (arginine vasopressin, AVP), and oxytocin (oxytocin, OXT) all play an important role in the regulation of stress response. It is worth noting that in the study of stress reactions, the use of anesthetics before animals is a common test method. However, the effects of the anesthetics on the results of the stress response have not been clearly concluded. It is reported that anesthetics can be used to inhibit the brain excitability, such as the N-Methyl-D-Aspartate, NMDA receptor subtype NR 2B, neuron type nicotinic acetylcholine receptor (neuronal-type nicotinic acetylcholine receptor, nnAChR), and activation of brain inhibitory receptors, such as gamma aminobutyric acid (Gamma amino butyric acid, GABA) A receptors, which affect brain power. So far, the common anesthetic was used before the sacrifice of experimental animals. Methods, such as whether intraperitoneal injection of pentobarbital sodium, or isoflurane inhalation anaesthesia, whether the results of the acute stress response study are unknown. This article aims to study the different ways of sacrificing animals, namely, direct end of the head sacrifice, intraperitoneal injection of pentobarbital, and disconnection after inhalation of isoflurane. The effects of head sacrifice on the results of acute stress response, including the effects on plasma stress hormone corticosterone (corticosterone, CORT), plasma sex hormone T and E2 levels, as well as the expression of mRNA in the hypothalamic stress related molecules such as CRH, AVP, OXT, as well as the effect of frontal stress related molecules such as NR2B, nnAChR, GABAAR mRNA. The male Sprague-Dawley (SD) rats were randomly divided into the sole electric shock (foot shock, FS) group and the control group. According to the method of sacrificing rats, the rats were further divided into subgroups: direct head sacrifice group, intraperitoneal injection of pentobarbital sodium after intraperitoneal injection of head sacrifice group and 6 groups after isoflurane inhalation anesthesia (a total of 6 groups). Plasma CORT was measured by enzyme linked immunosorbent assay, plasma T was measured by radioimmunoassay, plasma E2 was measured by enzyme immunoassay, and PCR (Quantitative reverse transcription PCR, Q-PCR) was used to determine hypothalamic stress related molecules CRH, AVP and OXT as well as OXT, as well as in the sample of blood, hypothalamus and frontal lobes. Changes in the expression of prefrontal stress related molecules NR2B, GABAAR and nnAChR-mRNA. Results: FS significantly increased plasma CORT level (P0.001) in the direct end of the head sacrifice group and after the inhalation of isoflurane, while in the intraperitoneal injection of pentobarbital sodium, the significant effect of FS on the plasma CORT level was not observed (P=0.132). In the control group, the abdominal cavity was in the control group. Intraperitoneal injection of saline or intraperitoneal injection of pentobarbital sodium significantly increased the level of plasma CORT (P=0.008, P=0.004). There was no significant difference in mRNA levels between sex hormones and brain stress related molecules (P > 0.132). Conclusion: intraperitoneal injection, not an anesthetic itself, leads to additional stress in animals. The plasma levels of plasma CORT, which was caused by acute FS stress, were "disappearing" between the stress group and the control group, thus disturbing the results. This type of anesthesia did not significantly affect the expression of plasma sex hormones or the expression of stress related molecules in the brain, mRNA, and isoflurane gas absorption. Anesthesia has no significant effect on acute stress response. From the perspective of animal ethics, sacrifice after isoflurane inhalation anesthesia is a better experimental method.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R749.4

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