本文選題：小型豬　切入點(diǎn)：替來他明　出處：《東北農(nóng)業(yè)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：小型豬復(fù)合麻醉劑(XFM)是課題組根據(jù)小型豬的生理特點(diǎn)和平衡麻醉理論,研制出的一種小型豬專用的復(fù)合麻醉劑,具有麻醉誘導(dǎo)時間短、麻醉維持時間適宜、副作用小的優(yōu)點(diǎn)。替來他明和曲馬多作為XFM的成份之一,均作用于動物的中樞神經(jīng)系統(tǒng),并且都具有確實(shí)的鎮(zhèn)痛效果。最新的研究證明:LKB1-AMPK-m TOR信號轉(zhuǎn)導(dǎo)通路中的關(guān)鍵蛋白參與了機(jī)體疼痛和神經(jīng)元興奮性的調(diào)節(jié),推測LKB1-AMPK-m TOR信號轉(zhuǎn)導(dǎo)通路可能參與了麻醉的鎮(zhèn)痛調(diào)控。所以本實(shí)驗通過給大鼠腹腔注射生理鹽水、鹽酸替來他明和鹽酸曲馬多,利用分子生物學(xué)技術(shù)檢測藥物注射后不同時間中樞神經(jīng)系統(tǒng)(大腦皮層、海馬、丘腦、小腦、腦干)中LKB1-AMPK-m TOR信號通路的關(guān)鍵蛋白基因的轉(zhuǎn)錄量和蛋白的磷酸化水平,進(jìn)而探討他們的鎮(zhèn)痛機(jī)制,從而推測XFM的全麻鎮(zhèn)痛機(jī)理。將54只SD大鼠隨機(jī)分為對照組(n=6)、麻醉組(n=24)和鎮(zhèn)痛組(n=24)。各組大鼠分別腹腔注射生理鹽水、鹽酸替來他明或鹽酸曲馬多后,對照組大鼠在注射生理鹽水后10 min頸椎脫臼處死,麻醉組和鎮(zhèn)痛組根據(jù)注射藥物后10 min、20 min、40 min和60 min分為四個亞組(n=6),分別在相應(yīng)時間點(diǎn)頸椎脫臼處死,并迅速采集大腦皮層、海馬、丘腦、小腦和腦干部位,利用RT-PCR檢測樣品中LKB1 mRNA、AMPKα1 m RNA、AMPKα2 m RNA和4EBP1m RNA的相對轉(zhuǎn)錄量,利用Western-blot方法檢測各樣品p-LKB1/LKB1、p-AMPK/AMPK和p-4EBP1/4EBP1蛋白磷酸化水平。實(shí)驗結(jié)果表明:(1)替來他明和曲馬多能使LKB1 m RNA、AMPKα1 m RNA和AMPKα2 m RNA的轉(zhuǎn)錄量極顯著性升高(p0.01),而抑制4EBP1 m RNA的轉(zhuǎn)錄量(p0.01)。(2)替來他明和曲馬多能促進(jìn)LKB1和AMPK的磷酸化水平(p0.01),相反抑制了4EBP1的磷酸化水平(p0.01)。(3)在大鼠的中樞神經(jīng)系統(tǒng)中,替來他明和曲馬多在海馬、丘腦、小腦以及腦干區(qū)表現(xiàn)出高效的調(diào)節(jié)作用,且多為藥物注射后的20 min和40 min。綜上,實(shí)驗得出結(jié)論:LKB1-AMPK-mTOR信號轉(zhuǎn)導(dǎo)通路參與了替來他明和曲馬多的麻醉、鎮(zhèn)痛調(diào)節(jié),而大鼠的海馬、小腦、丘腦、腦干可能是LKB1-AMPK-m TOR信號通路參與麻醉與鎮(zhèn)痛的靶位;通過激活LKB1-AMPK-mTOR信號通路作用于該藥物相對應(yīng)的靶蛋白上產(chǎn)生麻醉、鎮(zhèn)痛作用可能是替來他明和曲馬多的作用機(jī)制,這一研究結(jié)果對于深入揭示小型豬復(fù)合麻醉劑的鎮(zhèn)痛和麻醉機(jī)理奠定了堅實(shí)的基礎(chǔ)。
[Abstract]:The miniature pig compound anesthetic (XFM) is a special compound anesthetic for miniature pigs, which is developed by the research group according to the physiological characteristics and balanced anesthetic theory of miniature pigs. It has the advantages of short induction time and suitable maintenance time. The advantages of small side effects. Teletamine and tramadol, as one of the components of XFM, both act on the central nervous system of animals. Recent studies have shown that the key proteins in the TOR signal transduction pathway of 1: LKB1-AMPK-m participate in the regulation of pain and neuronal excitability. It is speculated that the LKB1-AMPK-m TOR signal transduction pathway may be involved in the analgesic regulation of anaesthesia. Therefore, in this experiment, the rats were injected intraperitoneally with normal saline, teletamine hydrochloride and tramadol hydrochloride. The transcription and phosphorylation of key protein genes of LKB1-AMPK-m TOR signaling pathway in central nervous system (cerebral cortex, hippocampus, thalamus, cerebellum, brainstem) at different time after drug injection were measured by molecular biological techniques. 54 SD rats were randomly divided into control group (n = 6), anesthesia group (n = 24) and analgesia group (n = 24). Rats in each group were given intraperitoneal injection of normal saline, teletamine hydrochloride or tramadol hydrochloride, respectively. The rats in the control group were killed 10 min after injection of normal saline. The anesthetic group and the analgesia group were divided into four subgroups according to the time of 10 minutes, 20 minutes, 40 min and 60 min after injection. The rats were killed at the corresponding time points, and the cerebral cortex was collected rapidly. In hippocampus, thalamus, cerebellum and brain stem, RT-PCR was used to detect the relative transcription of AMPK 偽 1 m RNA-AMPK 偽 2 m RNA and 4EBP1m RNA. The phosphorylation levels of p-LKB1 / AMPK and p-4EBP1/4EBP1 proteins in each sample were detected by Western-blot method. The results showed that teletamine and tramadol could significantly increase the transcription of LKB1 m RNAAMPK 偽 1 m RNA and AMPK 偽 2 m RNA and inhibit the transcription quantity of 4EBP1 m RNA. Lertamine and tramadol could promote the phosphorylation level of LKB1 and AMPK (p0.01), but inhibit the phosphorylation level of 4EBP1 (p0.01) in the central nervous system of rats. Teletamine and tramadol showed high regulatory effects in the hippocampus, thalamus, cerebellum and brain stem area, and most of them were 20 min and 40 mins after drug injection. It is concluded that the LKB1-AMPK-m TOR signal transduction pathway may be involved in the regulation of anesthesia and analgesia by teletamine and tramadol, while the hippocampus, cerebellum, thalamus and brain stem may be the targets of LKB1-AMPK-m TOR signaling pathway. By activating the LKB1-AMPK-mTOR signaling pathway to produce anesthesia on the corresponding target protein of the drug, the analgesic effect may be the mechanism of teletamine and tramadol. The results laid a solid foundation for further revealing the analgesic and anesthetic mechanism of miniature pig compound anesthetic.
【學(xué)位授予單位】：東北農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：S859.791

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