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目的考察噻吩诺啡慢性处理对大鼠海马区突触可塑性的影响,探讨药物对学习记忆(认知功能)的作用特点。方法大鼠噻吩诺啡慢性处理后,通过电生理学方法测定海马齿状回LTP的变化和免疫组化方法测定海马区学习记忆相关蛋白突触素含量的变化反映海马突触功能可塑性;通过电镜观察突触结构的超微变化并测定突触界面结构参数反映海马突触结构可塑性变化。结果①各药物慢性处理5 d,噻吩诺啡租大鼠在给予高频串刺激后,反映LTP现象的PS幅值显著增高至基线的(278±11)%,吗啡组大鼠为基线的(193±3)%,对照组为(152±6)%。②各处理大鼠在3 d,5 d海马脑区突触素的含量无明显变化;在8 d,与吗啡组比较,噻吩诺啡组大鼠海马突触素含量的明显升高(P<0.05),吗啡组大鼠海马突触素的含量与盐水对照组比较出现降低(P<0.05)。③各药物慢性处理14 d,噻吩诺啡组大鼠海马CA1区神经元胞核圆,核膜结构较清晰,极少数线粒体、内质网轻度扩张,肿胀;吗啡组大鼠海马CA1区神经元胞核大而圆,部分神经细胞核膜呈节段性结构不清楚,模糊,胞浆内线粒体及粗面内质网丰富,但有部分线粒体结构模糊,嵴消失,甚至空泡变性;盐水对照组大鼠海马CA1区结构正常。④各药物慢性处理14 d,与对照组相比,吗啡组、噻吩诺啡组三组大鼠突触活性区长度减小(P<0.05),吗啡组的PSD厚度明显减小(P<0.01);与吗啡组相比,噻吩诺啡组大鼠的PSD厚度增加及突触活性区长度增加(P<0.05),其他突触界面结构参数组间差异无显著性(P>0.05)。结论噻吩诺啡慢性处理对突触可塑性有影响,但其损害程度远小于吗啡,这可能是噻吩诺啡的低依赖性且区别于吗啡的突触机制之一。
Objective To investigate the effect of chronic treatment with thienorphine on synaptic plasticity in hippocampus of rats and explore the effect of drugs on learning and memory (cognitive function). Methods The changes of hippocampal dentate gyrus LTP and the content of synaptophysin in hippocampus were detected by electrophysiological method after the chronic treatment of thienorphine in hippocampus. The changes of hippocampal synaptic plasticity were observed by electron microscopy Synaptic ultrastructure changes and determination of synaptic interface structure parameters reflect changes in hippocampal synaptic plasticity. Results ① After chronic treatment of each drug for 5 days, the PS amplitude of LTP was significantly increased to (278 ± 11)% of the baseline in rats administered thienorphine after high-frequency stimulation and 193 ± 3)%, while the control group was (152 ± 6)%. ② The contents of synaptophysin in hippocampus of rats on the 3rd and 5th day were not significantly different. On the 8th day, compared with the morphine group, the content of synaptophysin in the hippocampus of the thiophenetin group was significantly increased (P < 0.05). The content of hippocampal synaptophysin in morphine group was lower than that in saline control group (P <0.05). ③ After chronic treatment of each drug for 14 days, neurons in the hippocampus CA1 of thienorphine group had a round nucleus and a clear nuclear membrane structure, few mitochondria and endoplasmic reticulum were mildly dilated and swollen. In the morphine group, the hippocampal CA1 neurons Large round nuclei, some neuronal nuclear membrane segmental structure is unclear, fuzzy, rich in mitochondria and rough endoplasmic reticulum in the cytoplasm, but some mitochondrial structure fuzzy, disappeared cristae, and even vacuolar degeneration; saline control The structure of hippocampus CA1 in rats was normal. (4) Compared with the control group, the length of synaptic active region in morphine group and thienorphine group decreased (P <0.05), and PSD of morphine group decreased significantly (P <0.01) ). Compared with the morphine group, the PSD of thienorphine group increased and the length of the synaptic active region increased (P <0.05). There was no significant difference in other synaptic interface parameters (P> 0.05). Conclusion Chronic treatment with thienorphine has an effect on synaptic plasticity, but its damage is far less than that of morphine. This may be one of the synaptic mechanisms that is a low dependence of thienorphine and different from morphine.