本文選題：強(qiáng)迫游泳 + 抑郁癥��； 參考：《中南大學(xué)》2013年博士論文

【摘要】：抑郁癥會(huì)使心血管疾病的發(fā)病率升高,其機(jī)制的研究仍處于探索之中。慢性輕度不可預(yù)見性應(yīng)激(CUMS)模型是一種廣泛使用的抑郁癥模型,在這里我們采用一個(gè)GC/MS為基礎(chǔ)的代謝輪廓分析方法,探索抑郁模型大鼠心肌代謝輪廓的變化。利用主成分分析(PCA)和偏最小二乘判別分析(PLS-DA)來揭示抑郁模型和對(duì)照組之間的差異。結(jié)果發(fā)現(xiàn)具有心臟保護(hù)作用的分子—谷氨酰胺(P=0.019)和肌苷(P=0.013),作為心臟主要能源的分子—脂肪酸(9,12-十八碳二烯酸,p=0.002；棕櫚酸,P=0.006；硬脂酸,P=0.030)和合成心肌膠原分子的前體—脯氨酸(P=0.036)在抑郁模型組中下調(diào)。 根據(jù)心肌代謝組學(xué)結(jié)果并結(jié)合文獻(xiàn),我們推測(cè)糖脂代謝、調(diào)節(jié)糖脂代謝的脂聯(lián)素以及乙醛脫氫酶2(ALDH2)可能在抑郁心血管疾病共病中發(fā)揮作用。采用CUMS抑郁模型,觀測(cè)其體內(nèi)糖脂代謝、乙醛脫氫酶2和脂聯(lián)素水平的變化。此外研究了舍曲林對(duì)上述指標(biāo)的影響。CUMS模型組大鼠糖水偏好量和海馬腦源性神經(jīng)營養(yǎng)因子(BDNF)明顯降低,說明抑郁模型成功建立。CUMS降低了血清脂聯(lián)素、高密度脂蛋白膽固醇(HDL-C)、總膽固醇(TC)、甘油三酯(TG)、游離脂肪酸(FFA)的水平。舍曲林治療后顯著恢復(fù)了血清脂聯(lián)素、HDL-C的水平。在海馬中發(fā)現(xiàn)脂聯(lián)素mRNA,這表明脂聯(lián)素可能在海馬中表達(dá)；同時(shí)海馬脂聯(lián)素水平降低,而其受體AdipoR1和AdipoR2顯著上調(diào)以補(bǔ)償脂聯(lián)素的不足；海馬中ALDH2水平升高,其在抑郁發(fā)病中的作用尚不清楚。在心肌中,脂聯(lián)素蛋白水平也顯著降低,但其受體AdipoR1和AdipoR2以不同的趨勢(shì)調(diào)控(AdipoR1減少和AdipoR2增加)；具有心血管保護(hù)作用的ALDH2顯著降低。舍曲林治療后CUMS組這些變化在一定程度上恢復(fù)了。綜上所述,本研究證明應(yīng)激下調(diào)了血清和心肌中HDL-C、脂聯(lián)素和ALDH2的水平,增加了抑郁癥并發(fā)心血管病的風(fēng)險(xiǎn)。舍曲林治療抑郁癥的同時(shí),有潛在的保護(hù)心血管系統(tǒng)的作用。 目前尚未見到運(yùn)動(dòng)干預(yù)抑郁模型代謝組的報(bào)道。本實(shí)驗(yàn)采用超高效液相色譜質(zhì)譜聯(lián)用技術(shù)(UPLC-MS)技術(shù),結(jié)合PLS-DA高維統(tǒng)計(jì)分析,探討強(qiáng)迫游泳對(duì)健康大鼠和抑郁模型大鼠血漿和尿液代謝輪廓的影響,觀察強(qiáng)迫游泳對(duì)抑郁心血管疾病共病因子的影響。結(jié)果顯示每天70分鐘的強(qiáng)迫游泳造成了正常大鼠糖水偏好量的降低,以及海馬中BDNF水平的下調(diào)；而另一方面,相對(duì)抑郁模型強(qiáng)迫游泳又顯著上調(diào)了糖水偏好量和BDNF的水平。四組PLS-DA的代謝輪廓明顯分開,模型第一個(gè)主成分主要體現(xiàn)了強(qiáng)迫游泳和CUMS對(duì)代謝物的同向調(diào)節(jié)作用,而第二個(gè)主成分則顯示了二者的反向調(diào)節(jié)作用。通過S-plot篩選生物標(biāo)志物以及糖脂生化檢查,發(fā)現(xiàn)強(qiáng)迫游泳恢復(fù)了模型大鼠下降的脂聯(lián)素水平和上調(diào)的葡萄糖水平。HDL-C、總膽固醇、溶血磷脂酰膽堿、纈氨酸、肌酐、色氨酸、苯丙氨酸等在空白組和模型組中有顯著差異。圖26幅,表7個(gè),正文參考文獻(xiàn)184篇。
[Abstract]:Depression will increase the incidence of cardiovascular disease, its mechanism is still under exploration. Chronic mild unpredictable stress (CUMS) model is a widely used depression model. Here we use a GC / MS based metabolic profile analysis method to explore the changes of myocardial metabolic profile in depression model rats. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DAA) were used to reveal the difference between the depression model and the control group. The results showed that the heart protective molecule (Glutamine P0. 019) and inosine (P0. 013), which were the main energy of heart, were found to be the main energy of the heart-fatty acid 9, 12-octadecadienoic acid, P0. 002, palmitic acid, P0. 006, and inosine P0. 013, respectively. P0. 030) and proline, a precursor of myocardial collagen, were down-regulated in depression model group. Based on the results of myocardial metabolism and the literature we speculated that glycolipid metabolism adiponectin which regulates glycolipid metabolism and acetaldehyde dehydrogenase (ALDH2) may play a role in depression cardiovascular disease. The glucose and lipid metabolism, acetaldehyde dehydrogenase 2 and adiponectin levels were measured by CUMS depression model. In addition, the effects of sertraline on the above indexes were studied. In the CUMS model group, the amount of glucose water preference and brain-derived neurotrophic factor (BDNF) in the hippocampus were significantly decreased, indicating that the successful establishment of the depression model, .CUMS, decreased the serum adiponectin. High density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TGN), free fatty acid (FFA). Sertraline significantly recovered the serum adiponectin level of HDL-C after treatment. Adiponectin mRNAs were found in the hippocampus, indicating that adiponectin may be expressed in the hippocampus, and the level of adiponectin in hippocampus decreased, while its receptors AdipoR1 and AdipoR2 increased significantly to compensate for the deficiency of adiponectin. Its role in the pathogenesis of depression is unclear. The level of adiponectin protein also decreased significantly in myocardium, but its receptors AdipoR1 and AdipoR2 regulated the decrease of AdipoR1 and the increase of AdipoR2 in different trends, while ALDH2, which had cardiovascular protective effect, decreased significantly. These changes recovered to some extent in the CUMS group after sertraline treatment. In conclusion, this study demonstrated that stress down-regulated the levels of HDL-C, adiponectin and ALDH2 in serum and myocardium, and increased the risk of depression complicated with cardiovascular disease. Sertraline has the potential to protect the cardiovascular system while treating depression. At present, there is no report of metabolic group of exercise intervention depression model. The effect of forced swimming on plasma and urine metabolic profile in healthy and depressed rats was studied by using UPLC-MS and high dimensional statistical analysis of PLS-DA. To observe the effect of forced swimming on cofactors of depression and cardiovascular disease. The results showed that forced swimming for 70 minutes per day resulted in the decrease of sugar water preference and the down-regulation of BDNF level in the hippocampus of normal rats, and on the other hand, forced swimming in the depression model significantly up-regulated the glucose water preference and BDNF levels. The metabolic profile of PLS-DA in the four groups was obviously separated. The first principal component of the model mainly reflected the codirectional regulation of the metabolites by forced swimming and CUMS, while the second principal component showed the reverse regulation of the two. By S-plot screening of biomarkers and glycolipid biochemical tests, it was found that forced swimming restored the decreased adiponectin level and up-regulated glucose level. HDL-C, total cholesterol, lysophosphatidylcholine, valine, creatinine, tryptophan, total cholesterol, creatinine, tryptophan, total cholesterol, There were significant differences in phenylalanine between blank group and model group. There are 26 figures, 7 tables and 184 references.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R749.4;R-332

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本文編號(hào)：2030575