【摘要】：目的:探討異氟醚早期干預對條件恐懼大鼠恐懼記憶及海馬內源性大麻素水平的影響。方法:以巴甫洛夫條件恐懼反射理論為基礎,建立大鼠條件恐懼模型,模擬大鼠創(chuàng)傷后應激障礙(posttraumatic stress disorder,PTSD)恐懼記憶,高效液相色譜質譜分析和RT-PCR方法檢測模型大鼠海馬內源性大麻素2-AG(2-arachidonoylglycerol)、AEA(N-arachidonoylethanolamine)含量,行為學方法分析大鼠僵立時間,行為檢測前給予異氟醚干預對海馬內源性大麻素水平及大鼠僵立時間的影響,然后海馬或者腹腔給予內源性大麻素受體1拮抗劑AM281,再次記錄大鼠行為學表現(xiàn)。結果:條件恐懼模型大鼠的僵立時間與正常大鼠相比明顯增加(P0.05)AEA水解酶FAAH(fatty acid amide hydrolase,FAAH)和2-AG合成酶DAGL(diacylglycerol lipase,DAGL)mRNA水平與正常大鼠比較無差別(P0.05),而2-AG水解酶MAGL(monoacylglycerol lipase,MAGL)mRNA水平明顯升高(P0.05);異氟醚干預提高了模型大鼠海馬2-AG水平(P0.05),減少了應激大鼠的僵立時間(P0.05)。海馬內或者腹腔給予AM281均可抑制異氟醚對應激大鼠僵立時間的影響。結論:異氟醚通過海馬內源性大麻素2-AG干預創(chuàng)傷后應激障礙模型大鼠的恐懼記憶的形成。
[Abstract]:Aim: to investigate the effects of early intervention of isoflurane on fear memory and endogenous cannabinoid level in hippocampus of conditioned fear rats. Methods: based on Pavlov's theory of conditioned fear reflex, a model of conditioned fear in rats was established to simulate the fear memory in rats with post-traumatic stress disorder (posttraumatic stress disordersPTSD). The contents of endogenous cannabinoid 2-AG (2-arachidonoylglycerol) and N-arachidonoylethanolamine (N-arachidonoylethanolamine) in hippocampus of model rats were detected by HPLC / MS and RT-PCR respectively. The effects of isoflurane on endogenous cannabinoid level and stiffness time in hippocampus were observed before behavior test, and then AM281, an endogenous cannabinoid receptor 1 antagonist, was given to hippocampus or intraperitoneally. The behavioral manifestations of rats were recorded again. Results: the stiffness time of conditioned fear rats was significantly higher than that of normal rats (P0.05), and the mRNA levels of 2-AG synthase DAGL (diacylglycerol lipase dagl) were not significantly different from those of normal rats (P0.05), but the monoacylglycerol lipase MAGL mRNA levels were significantly increased (P0.05). The intervention of fluoride increased the level of 2-AG in hippocampus of model rats (P0.05), and decreased the time of stiffness (P0.05). Both intrahippocampal and intraperitoneal administration of AM281 could inhibit the effect of isoflurane on the stiffness time of stress rats. Conclusion: isoflurane interferes with the formation of fear memory in posttraumatic stress disorder rats through endogenous cannabinoid 2-AG in hippocampus.
【作者單位】： 西安第三醫(yī)院急診科;第四軍醫(yī)大學西京醫(yī)院心身科;
【基金】：國家自然科學基金(81671343)
【分類號】：R-332;R749.5
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本文編號：2137120