XFM及其頡頏劑對大鼠不同腦JNK3MAPK信號轉(zhuǎn)導(dǎo)通路的影響
發(fā)布時間：2018-10-09 21:46
【摘要】：本實驗旨在研究小型豬復(fù)合麻醉劑(XFM)及其頡頏劑對大鼠不同腦區(qū)JNK3 MAPK信號轉(zhuǎn)導(dǎo)通路的影響,探討XFM及其頡頏劑發(fā)揮麻醉和催醒交互作用機(jī)制,以便完善對麻醉與催醒機(jī)制的認(rèn)識,為研制、推廣新型藥物及更好地指導(dǎo)臨床實踐提供理論依據(jù)。將78只SD大鼠隨機(jī)分為麻醉組(M組)、頡頏劑組(X組)和麻醉劑與頡頏劑交互組(MX組)。M組又分為5個亞組,分別為C1組(對照組)、M1組(注射XFM后翻正反射消失即刻)、M2組(注射XFM后翻正反射消失后1h)、M3組(注射XFM后翻正反射恢復(fù)即刻)和M4組(注射XFM后翻正反射恢復(fù)后1h);X組又分為3個亞組,分別為C2組(對照組)、X1組(注射小型豬復(fù)合麻醉頡頏劑5min)和X2組(注射小型豬復(fù)合麻醉頡頏劑1h);MX組又分為5個亞組,分別為C3組(對照組),MX1組(注射XFM,翻正反射消失時立即注射小型豬復(fù)合麻醉頡頏劑,翻正反射恢復(fù)即刻)、MX2組(翻正反射消失時立即注射XFM復(fù)合頡頏劑,翻正反射恢復(fù)后1h);MX3組(翻正反射消失后1h,注射XFM復(fù)合頡頏劑,翻正反射恢復(fù)即刻);MX4組(翻正反射消失后1h,注射XFM復(fù)合頡頏劑,翻正反射恢復(fù)后1h);各組大鼠到達(dá)預(yù)訂時間點后即刻斷頭處死,分離大腦皮層、小腦、海馬、腦干和丘腦,用實時熒光定量PCR方法檢測β-arrestin2基因mRNA的相對轉(zhuǎn)錄量。用Western blot的方法檢測β-arrestin2、p-JNK和p-ATF-2蛋白的相對表達(dá)量。實驗結(jié)果表明:(1)麻醉劑組,大鼠大腦皮層、小腦中β-arrestin2 mRNA相對表達(dá)顯著降低,而海馬、腦干和丘腦中則顯著升高;大腦皮層、小腦和海馬中β-arrestin2蛋白、p-JNK蛋白相對表達(dá)量均顯著降低,而腦干和丘腦中則顯著升高;大鼠各腦區(qū)p-ATF-2蛋白的相對表達(dá)量在小腦和丘腦中顯著升高,在海馬中顯著降低,而大腦皮層與腦干中該蛋白均無顯著變化。(2)頡頏劑組,大鼠大腦皮層、小腦中的β-arrestin2 mRNA及其蛋白相對表達(dá)量顯著升高,而腦干、丘腦中則顯著降低,海馬中β-arrestin2 mRNA顯著降低但其蛋白則顯著升高;大腦皮層、小腦和海馬中p-JNK蛋白、p-ATF-2蛋白變化趨勢與β-arrestin2蛋白一致。(3)麻醉劑與頡頏劑交互作用組,大鼠在早期催醒中大腦皮層、小腦、海馬、腦干和丘腦中β-arrestin2 mRNA的相對表達(dá)量顯著降低,晚期催醒中大腦和小腦β-arrestin2 mRNA的相對表達(dá)量顯著升高,海馬、腦干和丘腦中則顯著降低;而β-arrestin2蛋白的相對表達(dá)量在大腦皮層、海馬中顯著降低,在小腦、腦干與丘腦中則顯著升高;p-JNK蛋白的相對表達(dá)量在大腦皮層、小腦和海馬中顯著升高,在腦干、丘腦中顯著降低;p-ATF-2蛋白的相對表達(dá)量在海馬顯著升高,在丘腦顯著降低,但在其他腦區(qū)無顯著變化。綜上所述,XFM可以抑制β-arrestin2蛋白、p-JNK蛋白和p-ATF-2蛋白在大鼠海馬中的表達(dá)并增強(qiáng)這三種蛋白在大鼠丘腦中的表達(dá),小型豬復(fù)合麻醉頡頏劑作用與XFM相反,JNK3 MAPK信號轉(zhuǎn)導(dǎo)通路是XFM及小型豬復(fù)合麻醉頡頏劑分別發(fā)揮麻醉與催醒作用的重要途徑;β-arrestin2蛋白可能是JNK3 MAPK信號轉(zhuǎn)導(dǎo)通路被XFM及小型豬復(fù)合麻醉頡頏劑激活的關(guān)鍵位點。小型豬復(fù)合麻醉頡頏劑不能完全逆轉(zhuǎn)XFM對JNK3 MAPK信號轉(zhuǎn)導(dǎo)通路的影響,該通路不是XFM產(chǎn)生麻醉作用及小型豬復(fù)合麻醉頡頏劑產(chǎn)生催醒作用的唯一途徑。
[Abstract]:The purpose of this experiment was to study the effect of XFM and its anti-inflammatory agent on the signal transduction pathway of JNK3 MAPK in different brain regions of rats. It provides a theoretical basis for the promotion of new drugs and better guiding clinical practice. Seventy-eight SD rats were randomly divided into anesthesia group (group M), group (X group) and anesthetic agent group (MX group). The M groups were divided into 5 subgroups, C1 (control group), M1 group (after injection XFM reverse reflex disappeared), M2 group (injection XFM backward positive reflection disappeared 1h), M3 group (injection XFM backward positive reflex recovery immediately) and M4 group (after injection XFM reverse reflex recovery 1h); The X group was divided into three subgroups: group C2 (control group), group X1 (injection minipig compound anesthesia agent for 5min) and X2 group (injection minipig compound anesthesia agent for 1h); MX group was divided into 5 subgroups, C3 (control group) and MX1 group (injection XFM, respectively). Immediate injection of small-sized pig compound anesthesia (anti-inflammatory agent, reverse reflex recovery), MX2 group (immediate injection of XFM composite anti-inflammatory agent after reverse reflex recovery), MX3 group (1h after reverse reflex disappearance), MX3 group (1h after disappearance of flip reflex), and injection of XFM compound anesthetic agent, Revert reflex (immediately); group MX4 (1h after reversal reflex disappearance, injection of XFM compound eye drops, 1h after reverse reflex recovery); end decapitation immediately after arrival of each group of rats, separate cerebral cortex, cerebellum, hippocampus, brain stem and thalamus, The relative amounts of mRNA were detected by real-time fluorescence quantitative PCR. The relative expression of p27-arrestin2, p-JNK and p-ATF-2 protein was detected by Western blot. The results showed that: (1) The relative expression of p27-arrestin2 mRNA in the rat cerebral cortex and the cerebellum was significantly decreased, while in the hippocampus, the brain stem and the thalamus, the relative expression level was significantly decreased in the cerebral cortex, the cerebellum and the hippocampus. The relative expression of p-ATF-2 protein in the brain regions of rats increased significantly in the cerebellum and thalamus, significantly decreased in the hippocampus and no significant changes in the protein in the cerebral cortex and the brain stem. (2) The relative expression of p27-arrestin2 mRNA and its protein in the cerebral cortex and cerebellum of the rat cerebral cortex and the cerebellum increased significantly, while in the brain stem and thalamus, the expression of p27-arrestin2 mRNA in the hippocampus was significantly reduced, but its protein increased significantly; the p-JNK protein in the cerebral cortex, cerebellum and hippocampus, The change trend of p-ATF-2 protein was consistent with that of p27-arrestin2 protein. (3) The relative expression of OPG-arrestin2 mRNA in the cerebral cortex, cerebellum, hippocampus, brain stem and thalamus was significantly decreased in the early awakening of the rats. The relative expression of p-JNK increased significantly in the cerebral cortex and hippocampus, and the relative expression of p-JNK increased significantly in the cerebral cortex, cerebellum and hippocampus, and in the brain stem, There was a significant decrease in the thalamus; the relative expression of p-ATF-2 protein increased significantly in the hippocampus, significantly decreased in thalamus, but there was no significant change in other brain regions. In conclusion, XFM can inhibit the expression of p27-arrestin2 protein, p-JNK protein and p-ATF-2 protein in the hippocampus of rats and enhance the expression of these three proteins in the thalamus of rats. The MAPK signal transduction pathway of JNK3 is an important way for XFM and small pig compound anesthesia to play an important role in anesthesia and awaking. The p38-arrestin2 protein may be the key site of the activation of the JNK3 MAPK signal transduction pathway by XFM and small pig compound anesthesia. The effect of XFM on the signal transduction pathway of JNK3 MAPK can not be completely reversed by a small pig compound anesthesia and anti-inflammatory agent.
【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】：2015
【分類號】：S865.1;S857.124
本文編號：2260898
[Abstract]:The purpose of this experiment was to study the effect of XFM and its anti-inflammatory agent on the signal transduction pathway of JNK3 MAPK in different brain regions of rats. It provides a theoretical basis for the promotion of new drugs and better guiding clinical practice. Seventy-eight SD rats were randomly divided into anesthesia group (group M), group (X group) and anesthetic agent group (MX group). The M groups were divided into 5 subgroups, C1 (control group), M1 group (after injection XFM reverse reflex disappeared), M2 group (injection XFM backward positive reflection disappeared 1h), M3 group (injection XFM backward positive reflex recovery immediately) and M4 group (after injection XFM reverse reflex recovery 1h); The X group was divided into three subgroups: group C2 (control group), group X1 (injection minipig compound anesthesia agent for 5min) and X2 group (injection minipig compound anesthesia agent for 1h); MX group was divided into 5 subgroups, C3 (control group) and MX1 group (injection XFM, respectively). Immediate injection of small-sized pig compound anesthesia (anti-inflammatory agent, reverse reflex recovery), MX2 group (immediate injection of XFM composite anti-inflammatory agent after reverse reflex recovery), MX3 group (1h after reverse reflex disappearance), MX3 group (1h after disappearance of flip reflex), and injection of XFM compound anesthetic agent, Revert reflex (immediately); group MX4 (1h after reversal reflex disappearance, injection of XFM compound eye drops, 1h after reverse reflex recovery); end decapitation immediately after arrival of each group of rats, separate cerebral cortex, cerebellum, hippocampus, brain stem and thalamus, The relative amounts of mRNA were detected by real-time fluorescence quantitative PCR. The relative expression of p27-arrestin2, p-JNK and p-ATF-2 protein was detected by Western blot. The results showed that: (1) The relative expression of p27-arrestin2 mRNA in the rat cerebral cortex and the cerebellum was significantly decreased, while in the hippocampus, the brain stem and the thalamus, the relative expression level was significantly decreased in the cerebral cortex, the cerebellum and the hippocampus. The relative expression of p-ATF-2 protein in the brain regions of rats increased significantly in the cerebellum and thalamus, significantly decreased in the hippocampus and no significant changes in the protein in the cerebral cortex and the brain stem. (2) The relative expression of p27-arrestin2 mRNA and its protein in the cerebral cortex and cerebellum of the rat cerebral cortex and the cerebellum increased significantly, while in the brain stem and thalamus, the expression of p27-arrestin2 mRNA in the hippocampus was significantly reduced, but its protein increased significantly; the p-JNK protein in the cerebral cortex, cerebellum and hippocampus, The change trend of p-ATF-2 protein was consistent with that of p27-arrestin2 protein. (3) The relative expression of OPG-arrestin2 mRNA in the cerebral cortex, cerebellum, hippocampus, brain stem and thalamus was significantly decreased in the early awakening of the rats. The relative expression of p-JNK increased significantly in the cerebral cortex and hippocampus, and the relative expression of p-JNK increased significantly in the cerebral cortex, cerebellum and hippocampus, and in the brain stem, There was a significant decrease in the thalamus; the relative expression of p-ATF-2 protein increased significantly in the hippocampus, significantly decreased in thalamus, but there was no significant change in other brain regions. In conclusion, XFM can inhibit the expression of p27-arrestin2 protein, p-JNK protein and p-ATF-2 protein in the hippocampus of rats and enhance the expression of these three proteins in the thalamus of rats. The MAPK signal transduction pathway of JNK3 is an important way for XFM and small pig compound anesthesia to play an important role in anesthesia and awaking. The p38-arrestin2 protein may be the key site of the activation of the JNK3 MAPK signal transduction pathway by XFM and small pig compound anesthesia. The effect of XFM on the signal transduction pathway of JNK3 MAPK can not be completely reversed by a small pig compound anesthesia and anti-inflammatory agent.
【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】：2015
【分類號】：S865.1;S857.124
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