异氟醚通过海马内源性大麻素调节条件恐惧大鼠恐惧记忆
发布时间：2018-07-22 10:26
【摘要】：目的:探讨异氟醚早期干预对条件恐惧大鼠恐惧记忆及海马内源性大麻素水平的影响。方法:以巴甫洛夫条件恐惧反射理论为基础,建立大鼠条件恐惧模型,模拟大鼠创伤后应激障碍(posttraumatic stress disorder,PTSD)恐惧记忆,高效液相色谱质谱分析和RT-PCR方法检测模型大鼠海马内源性大麻素2-AG(2-arachidonoylglycerol)、AEA(N-arachidonoylethanolamine)含量,行为学方法分析大鼠僵立时间,行为检测前给予异氟醚干预对海马内源性大麻素水平及大鼠僵立时间的影响,然后海马或者腹腔给予内源性大麻素受体1拮抗剂AM281,再次记录大鼠行为学表现。结果:条件恐惧模型大鼠的僵立时间与正常大鼠相比明显增加(P0.05)AEA水解酶FAAH(fatty acid amide hydrolase,FAAH)和2-AG合成酶DAGL(diacylglycerol lipase,DAGL)mRNA水平与正常大鼠比较无差别(P0.05),而2-AG水解酶MAGL(monoacylglycerol lipase,MAGL)mRNA水平明显升高(P0.05);异氟醚干预提高了模型大鼠海马2-AG水平(P0.05),减少了应激大鼠的僵立时间(P0.05)。海马内或者腹腔给予AM281均可抑制异氟醚对应激大鼠僵立时间的影响。结论:异氟醚通过海马内源性大麻素2-AG干预创伤后应激障碍模型大鼠的恐惧记忆的形成。
[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.
【作者单位】： 西安第三医院急诊科;第四军医大学西京医院心身科;
【基金】：国家自然科学基金(81671343)
【分类号】：R-332;R749.5
，
本文编号：2137120
[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.
【作者单位】： 西安第三医院急诊科;第四军医大学西京医院心身科;
【基金】：国家自然科学基金(81671343)
【分类号】：R-332;R749.5
，
本文编号：2137120
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