本文關(guān)鍵詞： 抑郁癥 神經(jīng)可塑性 小分子糖苷 抗抑郁活性篩選　出處：《云南大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：抑郁癥是一種發(fā)病率高、危害嚴(yán)重的精神疾病。其發(fā)病機(jī)制復(fù)雜,目前學(xué)界提出的機(jī)制包括單胺假說、HPA軸假說、神經(jīng)營(yíng)養(yǎng)假說、炎癥因子假說、表觀遺傳假說和神經(jīng)可塑性假說等�，F(xiàn)有抗抑郁藥物主要包括選擇性5-羥色胺再攝取抑制劑(Selective serotonin reuptake inhibitors, SSRI)、選擇性5-羥色胺以及去甲腎上腺素再攝取抑制劑(Serotonin and norepinephrine reuptake inhibitors, SNRI)等。約30%的患者對(duì)現(xiàn)有藥物治療無(wú)響應(yīng)。而且,常用的抗抑郁藥物大多具有起效慢的缺陷,也存在很多副作用。開發(fā)新靶點(diǎn)新機(jī)理的抗抑郁藥已經(jīng)成為臨床迫切需要。傳統(tǒng)中藥仙茅中分離提取的苔黑酚葡萄糖苷具有改變突觸可塑性,增強(qiáng)實(shí)驗(yàn)動(dòng)物學(xué)習(xí)與記憶的藥理活性,是一類機(jī)制新穎的抗抑郁活性化合物。 本論文以苔黑酚葡萄糖苷為先導(dǎo)化合物,通過更換苷元部分和糖基部分,以及變化苷鍵構(gòu)型,對(duì)其進(jìn)行進(jìn)一步分子結(jié)構(gòu)優(yōu)化,共合成了21個(gè)化合物。所有化合物結(jié)構(gòu)均得到1H-NMR、13C-NMR和HRMS等數(shù)據(jù)的證實(shí)。 本研究采取小鼠懸尾實(shí)驗(yàn)(TST)和小鼠強(qiáng)迫游泳實(shí)驗(yàn)(FST)動(dòng)物模型,利用原型化合物苔黑酚葡萄糖苷(OR-1)作參照,對(duì)合成的3個(gè)化合物OR-A、OR-G、 OR-X進(jìn)行抗抑郁活性篩選。結(jié)果顯示：化合物OR-1、OR-A、OR-G、OR-X在灌胃20mg/kg劑量下沒有產(chǎn)生抗抑郁活性�；衔颫R-A (20mg/kg, i.g.)延長(zhǎng)懸尾實(shí)驗(yàn)的不動(dòng)時(shí)間,對(duì)強(qiáng)迫游泳實(shí)驗(yàn)的不動(dòng)時(shí)間無(wú)影響；而化合物OR-G和OR-X (20mg/kg, i.g.)顯著延長(zhǎng)了小鼠懸尾實(shí)驗(yàn)和強(qiáng)迫游泳實(shí)驗(yàn)的不動(dòng)時(shí)間(P0.01),提示這兩個(gè)化合物可能具有鎮(zhèn)靜作用。
[Abstract]:Depression is a high incidence of serious mental disease. Its pathogenesis is complex, the academic circles put forward the mechanism including the monoamine hypothesis, HPA axis hypothesis, neurotrophic hypothesis hypothesis, inflammatory factors, epigenetic hypothesis and neural plasticity hypothesis. Existing antidepressant drugs mainly include selective serotonin re 5- (Selective serotonin reuptake inhibitors uptake inhibitor, SSRI 5-), selective serotonin and norepinephrine reuptake inhibitor (Serotonin and norepinephrine reuptake inhibitors, SNRI). About 30% of the patients with no response to existing drugs. Moreover, antidepressants have slow onset of defects, there are many side effects. The mechanism of the development of a new target of antidepressants has become urgent clinical needs. The extraction and separation of traditional Chinese medicine Xianmao in orcinol glucoside has the change of synaptic plasticity Sex, enhancing the pharmacological activity of learning and memory of experimental animals, is a kind of novel antidepressant compound.
The orcinol glucoside as the lead compound, by replacing the aglycone and sugar moieties, and the change of glycoside bond configuration, further optimize the molecular structure on the 21 compounds were synthesized. The structures of all compounds were 1H-NMR, 13C-NMR and HRMS data confirmed.
This research adopts the mouse tail suspension test (TST) and mice forced swimming test (FST) animal model, using the prototype compound orcinol glucoside (OR-1) as a reference, OR-G of the 3 compounds OR-A, OR-X synthesis, screening of antidepressant activity. The results showed that compounds OR-1, OR-A, OR-G, OR-X have antidepressant activity in gastric lavage at a dose of 20mg/kg. Compound OR-A (20mg/kg, i.g.) prolonged immobility time in tail suspension test, the immobility time of the forced swimming test has no effect; and compounds OR-G and OR-X (20mg/kg, i.g.) significantly prolonged immobility time in tail suspension test and the forced swimming test (P0.01), suggesting that these two compounds may have a calming effect.

【學(xué)位授予單位】：云南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R914;R965

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