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目的:研究谷氨酸受体拮抗剂地卓西平对吗啡依赖大鼠部分脑区前脑啡肽(PENK)基因转录水平的影响。方法:18只雄性Sprague-Dawley大鼠随机等分吗啡组、干预组及对照组,每组6只。吗啡组大鼠腹腔注射吗啡,起始剂量5mg/kg,2次/d,逐日递增5mg,至第10天为50mg/kg;干预组大鼠每次注射吗啡前30分钟腹腔注射地卓西平0.075mg/kg;对照组按平行对照原则注射同体积的生理盐水。末次注射后3h取脑并冰冻切片,留取中脑腹侧被盖区(VTA)、伏隔核(NAc)、中脑导水管灰质(PAG)、杏仁核(AMG)、海马CA1区(HIPCA1)的切片。利用原位杂交及图像分析技术检测各脑区PENKmRNA的水平(吸光度A值)。结果:与对照组相比,吗啡组大鼠各脑区A值均明显降低,干预组大鼠在除AMG外的其它被检脑区也明显降低;与吗啡组相比,干预组大鼠VTA、NAc、AMG、HIPCA1区A值升高。结论:吗啡依赖大鼠多个脑区PENK基因表达明显下调,合并使用地卓西平可在一定程度上拮抗PENK基因表达的下调。
AIM: To investigate the effect of glutamate receptor antagonist dirhizepine on the transcriptional level of PENK in some brain regions of morphine-dependent rats. Methods: Eighteen male Sprague-Dawley rats were randomly divided into morphine group, intervention group and control group, with 6 rats in each group. Morphine group rats were injected morphine intraperitoneally, the initial dose of 5mg / kg, 2 times / d, day by day increase of 5mg, to the first 10 days of 50mg / kg; intervention group rats 30 minutes before each injection of morphine ip injection of z09075 mg / kg; control group according to the principle of parallel control injection of the same volume of saline. The brain was taken at 3h after the last injection and frozen sections were obtained. The ventral tegmental area (VTA), nucleus accumbens (NAc), midgut aquaporin (PAG), amygdala (AMG), hippocampal CA1 area ) Section. In situ hybridization and image analysis were used to detect the levels of PENK mRNA in each brain region (absorbance A value). Results: Compared with the control group, the A value of each brain area of morphine group was significantly lower than that of the control group, while the intervention group was also significantly reduced in other brain regions except AMG. Compared with the morphine group, the VTA , NAc, AMG, HIPCA1 area A value increased. CONCLUSION: The expression of PENK gene in multiple brain regions of morphine dependent rats was significantly down-regulated. Combined use of droperidol could antagonize the down-regulation of PENK gene expression to a certain extent.