【摘要】：實(shí)驗(yàn)?zāi)康模?咪達(dá)唑侖是一種經(jīng)典的短效苯二氮卓類(lèi)藥物,臨床上通常用于術(shù)前鎮(zhèn)靜。為明確咪達(dá)唑侖對(duì)中樞神經(jīng)系統(tǒng)中氨基酸類(lèi)神經(jīng)遞質(zhì),單胺類(lèi)神經(jīng)遞質(zhì)及ATP酶跨膜信號(hào)轉(zhuǎn)導(dǎo)系統(tǒng)、cAMP信號(hào)轉(zhuǎn)導(dǎo)通路和NO-cGMP信號(hào)轉(zhuǎn)導(dǎo)通路的影響,探討其發(fā)揮鎮(zhèn)靜作用的主要靶位,及參與麻醉的可能路徑。 實(shí)驗(yàn)方法： 本實(shí)驗(yàn)以胎鼠為實(shí)驗(yàn)對(duì)象,將90只胎鼠分為3組,每組設(shè)3個(gè)平行。根據(jù)在體實(shí)驗(yàn)測(cè)得咪達(dá)唑侖在大鼠血漿中的濃度范圍為5-60μg/ml,本實(shí)驗(yàn)選取3個(gè)濃度組,低劑量組3.41×10-3ug／ml,中劑量組5μg/ml,高劑量組60μg/ml采用直接細(xì)胞給藥的方式,于051015202530456090120min時(shí)采樣,采用質(zhì)譜檢測(cè)單胺類(lèi)神經(jīng)遞質(zhì),氨基酸類(lèi)神經(jīng)遞質(zhì),酶標(biāo)儀法測(cè)量信號(hào)轉(zhuǎn)導(dǎo)通路中ATP酶的活性,NO及NOS的含量,用ELISA測(cè)定cGMP和cAMP含量。 實(shí)驗(yàn)結(jié)果： 1、不同濃度的咪達(dá)唑侖能減少神經(jīng)元興奮性神經(jīng)遞質(zhì)的含量,增加抑制性神經(jīng)遞質(zhì)的含量。 2、不同濃度的瞇達(dá)唑侖對(duì)兒茶酚胺類(lèi)神經(jīng)遞質(zhì)和五羥色胺的作用趨勢(shì)是先升高后降低,對(duì)五羥吲哚乙酸的作用趨勢(shì)是先降低后升高。 3、不同濃度的咪達(dá)唑侖對(duì)ATP酶的影響是顯著降低,對(duì)NO和NOS的影響是顯著降低,對(duì)cAMP和cGMP的影響是先降低后升高再降低。 結(jié)論： 1咪達(dá)唑侖能降低興奮性神經(jīng)遞質(zhì)和單胺類(lèi)神經(jīng)遞質(zhì)的含量。 2咪達(dá)唑侖對(duì)ATP酶,cAMP和cGMP信號(hào)通路的作用是抑制性的。 3咪達(dá)唑侖的鎮(zhèn)靜機(jī)制可能與抑制興奮性神經(jīng)遞質(zhì),ATP酶,cAMP和cGMP信號(hào)通路有關(guān)。
[Abstract]:Objective: midazolam is a classic short-acting benzodiazepines and is commonly used for preoperative sedation. To elucidate the effects of midazolam on amino acid neurotransmitters, monoamine neurotransmitters, ATPase transmembrane signal transduction pathway and NO-cGMP signal transduction pathway in the central nervous system, and to explore the main targets of midazolam for sedation. And possible pathways involved in anesthesia. Methods: 90 fetal mice were divided into 3 groups with 3 parallel in each group. The concentration of midazolam in rat plasma was measured in vivo in the range of 5-60 渭 g / ml. In this experiment, three concentration groups were selected: low dose group (3.41 脳 10 ~ (-3) 渭 g / ml), medium dose group (5 渭 g / ml) and high dose group (60 渭 g/ml). Monoamine neurotransmitters and amino acid neurotransmitters were detected by mass spectrometry. The activity of ATPase no and NOS in signal transduction pathway were measured by enzyme label method. CGMP and camp were measured by Elisa. Results: 1. Midazolam at different concentrations can reduce the content of excitatory neurotransmitters in neurons. Increasing the content of inhibitory neurotransmitters. (2) the effect of different concentrations of midazolam on catecholamine neurotransmitters and serotonin increased first and then decreased. The effect of midazolam at different concentrations on ATPase, no and NOS was significantly decreased, and on camp and cGMP decreased first and then decreased. Conclusion: 1 midazolam can reduce the contents of excitatory neurotransmitters and monoamine neurotransmitters. 2 midazolam inhibits the ATP enzyme camp and cGMP signaling pathway. The sedative mechanism of zolam may be related to the inhibition of camp and cGMP signaling pathway.
【學(xué)位授予單位】：東北農(nóng)業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：S859.79

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