【摘要】 目的:利用盐酸哌替啶制备类帕金森病大鼠模型,测定血清中神经生化反应。方法:实验于2000-06/2003-06在辽宁省基础医学研究所(血清分析在中国医科大学科研中心液相色谱室)完成。选用Wistar健康成年大鼠36只,雄雌各半。随机分6组:帕金森病模型组:每日经腹腔内注射盐酸哌替啶20mg/kg,连续用药21d;盐酸哌替啶+纳络酮组:每日经腹腔注射盐酸哌替啶20mg/kg,再经腹腔注射纳络酮0.05mg/kg,连续用药21d;盐酸哌替啶+溴隐亭组:每日经腹腔注射盐酸哌替啶20mg/kg,再胃饲溴隐亭20mg/次,连续21d;治疗Ⅰ组:每日经腹腔注射盐酸哌替啶20mg/kg,连用21d后停药每日改用纳络酮0.015mg/kg,连用30d;治疗Ⅱ组:每日经腹腔注射盐酸哌替啶20mg/kg,连用21d后停药改用溴隐亭20mg/次胃饲,连用30d;对照组:经腹腔注射生理盐水与上述同等毫升数,连用21d。吸毒者血清由沈阳戒毒所提供,以健康人血清做对照。用高效液相-电化学检测器检测盐酸哌替啶、纳络酮及溴隐亭对大鼠血清中单胺类神经递质:多巴胺、去甲肾上腺素、5-羟色胺,高香草酸、5-羟吲哚乙酸含量的变化。结果:36只大鼠均进入结果分析,无脱落。①帕金森病模型组大鼠血中多巴胺含量明显低于对照组(P<0.05),去甲肾上腺素含量无明显变化(P>0.05)。②与帕金森病模型组比较,盐酸哌替啶+纳络酮组多巴胺含量明显升高(P<0.01),去甲肾上腺素含量亦明显升高(P<0.01);盐酸哌替啶+溴隐亭组多巴胺亦升高但差异不明显(P>0.05),去甲肾上腺素含量高于帕金森病模型组(P<0.05);治疗Ⅰ、Ⅱ组与帕金森病模型组比较,多巴胺含量明显升高(P<0.01,P<0.05),去甲肾上腺素亦明显升高(P<0.01,P<0.05)。结论:盐酸哌替啶对多巴胺神经元有选择性破坏作用。更多还原

【Abstract】 AIM: To prepare the Parkinson disease models in rats with meperidine hydrochloride,and measure the neural biochemical reaction in serum. METHODS: During June 2000 and June 2003,the experiment was conducted at Liaoning Institute of Basic Medical Sciences,while the serum analysis was done at Liquid Chromatography Room of Scientific Research Center of China Medical University. Thirty-six healthy adult Wistar rats of either sex were randomized into 6 groups: Parkinson disease model group: Intraperitoneal injection of 20 mg/kg meperidine hydrochloride was given every day,continuously for 21 days Experimental group Ⅰ: Intraperitoneal injection of 20 mg/kg meperidine hydrochloride and 0.05 mg/kg naloxone were given every day,continuously for 21 days Experimental group Ⅱ: Intraperitoneal injection of 20 mg/kg meperidine hydrochloride and 20 mg bromocriptine for one time by gavage were given every day,continuously for 21 days Treatment group Ⅰ: Intraperitoneal injection of 20 mg/kg meperidine hydrochloride was given every day,continuously for 21 days. Then 0.015 mg/kg naloxone was administrated every day,continuously for 30 days Treatment group Ⅱ: Intraperitoneal injection of 20 mg/kg meperidine hydrochloride was given every day,continuously for 21 days. Then 20 mg bromocriptine for one time by gavage was administrated every day,continuously for 30 days Control group: Equal saline was injected intraperitoneally for successive 21 days. The serum of drug addicts were provided by Shenyang Drug Rehabilitation Center,and in contrast with healthy human serum. High performance liquid chromatography-electrochemistry device (HPLC-ECD) was applied to detect the changes of monoamine neurotransmitters such as noradrenaline (NA),dopamine (DA),homovanillic acid (HVA),5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacctic acid (5-HIAA) in the serum of rats caused by meperidine hydrochloride,naloxone and bromocriptine. RESULTS: Totally 36 rats entered the result analysis without loss.1In Parkinson disease model group,the concentration of DA in the serum of rats was far lower than that in control group (P 1 0.05),whereas the concentration of NA had no change (P > 0.05).2Compared with Parkinson disease model group,the concentrations of DA and NA were obviously elevated in experimental group Ⅰ (P 1 0.01)In the experimental group Ⅱ,the concentration of DA also increased,but the difference was insignificant (P > 0.05),while the concentration of NA was higher than that in Parkinson disease model group Ⅰ (P 1 0.05) In contrast with treatment groupsⅠand Ⅱ,the concentrations of DA and NA were both decreased obviously in Parkinson disease model group (P 1 0.01,P 1 0.05). CONCLUSION: Meperidine hydrochloride can play a selectively destructive role in DA neuron.更多还原