本文選題：內(nèi)源性大麻素2-AG + 大麻素受體　； 參考：《蘭州大學(xué)》2014年博士論文

【摘要】：目的：鞘內(nèi)注射內(nèi)源性大麻素2-AG和大麻素受體CB1和CB2拮抗劑后,通過行為學(xué)和形態(tài)學(xué)實驗方法,觀察大麻素受體和脊髓背角神經(jīng)細(xì)胞在2-AG抑制福爾馬林誘導(dǎo)的炎性持續(xù)性痛過程中扮演的角色。 方法：通過大鼠足底注射福爾馬林(5%,50μl),建立炎性持續(xù)性痛動物模型,形態(tài)學(xué)觀察大麻素受體亞型(CB1和CB2)在脊髓背角的分布情況,進(jìn)一步觀察這兩個受體亞型與神經(jīng)細(xì)胞(星形膠質(zhì)細(xì)胞、小膠質(zhì)細(xì)胞和神經(jīng)元)的共存情況。行為學(xué)觀察鞘內(nèi)注射內(nèi)源性大麻素2-AG后,對福爾馬林誘導(dǎo)的自發(fā)性傷害性行為(舔咬爪和縮腿反射)的抑制效應(yīng)；鞘內(nèi)注射大麻素CB1、CB2受體拮抗劑(AM281或者AM630)后,觀察是否翻轉(zhuǎn)了內(nèi)源性大麻素2-AG的抑制效應(yīng)。 結(jié)果：鞘內(nèi)注射內(nèi)源性大麻素2-AG(1,10,100μg；注射劑量10μl)后,發(fā)現(xiàn),隨著2-AG藥物濃度的增加,抑制效應(yīng)逐漸增強(qiáng),但是不成劑量依賴關(guān)系,各處理組之間存在顯著性差異(比如對照組和不同劑量內(nèi)源性大麻素2-AG組)(舔咬爪,F(3,287)=64.963,P0.001；縮腿反射,F(3,287)=131.255,P0.001),時間點之間也存在顯著性差異(F(11,287)=14.580,P0.001；F(11,287)=11.250,,P0.001),藥物和時間之間存在交互作用(F(33,287)=5.663,P0.001；F(33,287)=1.737,P=0.010)。內(nèi)源性大麻素2-AG誘導(dǎo)的抑制效應(yīng)可以被預(yù)先鞘內(nèi)注射大麻素受體CB1受體拮抗劑AM281翻轉(zhuǎn),各處理組之間存在顯著性差異(舔咬爪,F(3,215)=58.322,P0.001；縮腿反射,F(2,215)=139.472,P0.001),時間點之間也存在顯著性差異(F(11,215)=19.150,P0.001；F(11,215)=16.816,P0.001),藥物和時間之間存在交互作用(F(22,215)=7.530,P0.001；F(22,215)=2.670,P0.001)。同樣,內(nèi)源性大麻素2-AG誘導(dǎo)的抑制效應(yīng)可以被預(yù)先鞘內(nèi)注射大麻素受體CB2受體拮抗劑AM630翻轉(zhuǎn),各處理組之間存在顯著性差異(舔咬爪,F(2,215)=57.085,P0.001；縮腿反射,F(2,215)=84.265,P0.001),時間點之間也存在顯著性差異(F(11,215)=19.032,P0.001；F(11,215)=14.019,P0.001),藥物和時間之間存在交互作用(F(22,215)=4.260,P0.001；F(22,215)=3.300,P0.001)。形態(tài)學(xué)的研究結(jié)果顯示,在完全空白大鼠(Naive),腰段脊髓背角的CB1受體主要在神經(jīng)元上表達(dá),在小膠質(zhì)細(xì)胞有少量表達(dá),而在星形膠質(zhì)細(xì)胞未見表達(dá)。在大鼠足底注射福爾馬林后,腰段脊髓背角的CB1受體仍主要在神經(jīng)原上表達(dá),在小膠質(zhì)細(xì)胞有少量表達(dá),同時在星形膠質(zhì)細(xì)胞也開始表達(dá)。在完全空白大鼠脊髓背角CB2受體不表達(dá),但是在足底注射福爾馬林后,CB2受體表達(dá)增多,并且主要與星形膠質(zhì)細(xì)胞和小膠質(zhì)細(xì)胞共表達(dá),跟神經(jīng)元有少量共表達(dá)。 結(jié)論：研究結(jié)果提示,內(nèi)源性大麻素2-AG主要通過直接或者間接的作用于脊髓背角神經(jīng)膠質(zhì)(星形膠質(zhì)細(xì)胞和小膠質(zhì)細(xì)胞)上的大麻素受體CB1和CB2發(fā)揮對福爾馬林誘導(dǎo)的傷害性行為抑制效應(yīng),而CB2受體可能在此過程中起主導(dǎo)作用。
[Abstract]:Objective: to study the behavior and morphology of endogenous cannabinoid 2-AG and cannabinoid receptor CB1 and CB2 antagonists after intrathecal injection.To observe the role of cannabinoid receptor and spinal dorsal horn neurons in the inhibition of formalin-induced inflammatory persistent pain by 2-AG.Methods: the inflammatory persistent pain model was established by injection of Rhizoma Formalinus formalin into the plantar of rats. The distribution of cannabinoid receptor subtypes CB1 and CB2 in the dorsal horn of spinal cord was observed by morphology.The coexistence of these two receptor subtypes with neurons (astrocytes, microglia and neurons) was further observed.To observe the inhibitory effect of intrathecal injection of endogenous cannabinoid 2-AG on formalin induced spontaneous nociceptive behavior (licking claw and leg reflex), and after intrathecal injection of cannabinoid CB1 and CB2 receptor antagonist AM281 or AM630.To observe whether the inhibitory effect of endogenous cannabinoid 2-AG was reversed.Results: after intrathecal injection of endogenous cannabinoid 2-AGN (10100 渭 g, dose 10 渭 l), it was found that the inhibitory effect was increased with the increase of 2-AG concentration, but not in a dose-dependent manner.The inhibitory effect induced by endogenous cannabinoid 2-AG can be reversed by intrathecal injection of cannabinoid receptor CB1 receptor antagonist AM281.There were significant differences among the treatment groups (licking claw nip, 58.322, P 0.001; leg reflexes, 139.472, P 0.001; F11215, 19.150, P 0.001, F11215, 16.816, P0.001, P 0.001, and the interaction between the drug and the time, F2221530, P0.001, 2.670, P0.001, P 0.001, P 0.001, P 0.001, P 0.001), and the interaction between the drug and the time was also found in the treatment group, and there was also a significant difference between the two groups (P 0.001), and there was also a significant difference between the two groups (P < 0.05), and there was also a significant difference between the two groups in the treatment time, and there was also a significant difference between the two groups. There was an interaction between the two drugs.Similarly, the inhibitory effect induced by endogenous cannabinoid 2-AG can be reversed by pre-intrathecal injection of cannabinoid receptor CB2 receptor antagonist AM630.The results of morphological study showed that the CB1 receptor in the lumbar spinal dorsal horn was mainly expressed in neurons, a little in microglia, but not in astrocytes.After formalin injection into the plantar of rats, the expression of CB1 receptor in the dorsal horn of lumbar spinal cord was still mainly expressed on neurogen, a little on microglia and also on astrocytes.There was no expression of CB2 receptor in the spinal dorsal horn of rats with complete blank, but the expression of CB2 receptor was increased after formalin injection into the plantar, mainly co-expressed with astrocytes and microglial cells, and a little coexpression with neurons.Conclusion: the results of the study suggest that,Endogenous cannabinoid 2-AG inhibits formalin induced nociceptive behavior mainly by directly or indirectly acting on cannabinoid receptors (CB1 and CB2) on spinal dorsal horn glia (astrocytes and microglia).CB2 receptors may play a leading role in this process.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R965

【共引文獻(xiàn)】

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2 鄒曉琴;廖芳;黃誠;;谷氨酸及其受體在神經(jīng)病理性痛中的作用[J];贛南醫(yī)學(xué)院學(xué)報;2014年01期

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