口服百草枯建立帕金森病模型及其评价研究.docVIP

口服百草枯建立帕金森病模型及其评价研究 罗烘权1，袁进1，徐名衬1，郑春华1，王玉珏1，吴丽红2，顾为望1 1南方医科大学实验动物中心，广东省广州市 510515；2广州医科大学附属口腔医院，广东省广州市510140 摘要 目的：通过模拟人类经消化道长期慢性暴露于百草枯的方式研究其对大鼠黑质纹状体系统的影响，建立大鼠帕金森病模型及对其进行评价。方法：将大鼠随机分为高剂量组（20mg/kg百草枯），中剂量组（10mg/kg百草枯），低剂量组（5mg/kg百草枯）和对照组（生理盐水），每组16只，连续灌胃4个月后运用行为学检测系统、中脑黑质部及肺部病理学观察、HPLC法检测纹状体多巴胺及其代谢物含量等进行分析及评价。结果：给药4个月后，与对照组相比，中剂量组大鼠反应迟钝、动作僵硬、四肢震颤、学习记忆能力减退（P0.01）、中脑黑质神经元细胞明显萎缩、纹状体中的多巴胺及高香草酸含量分别下降了20.0%（P0.01）和11.3%（P0.01）且肺组织有明显损伤；低剂量组与对照组相比上述变化不明显。结论：通过口服百草枯可建立具典型行为学变化和大脑黑质纹状体多巴胺能神经系统受损的大鼠帕金森病模型，这将为帕金森病的机制及防治研究提供理想的模型动物。 关键词 口服； 百草枯； 帕金森病； 大鼠 The study of establishing the model of Parkinsons disease and its evaluation by taking orally paraquat LUO Hong-quan1，YUAN Jin1，XU Ming-chen1，ZHENG Chun-hua1，WANG Yu-jue1，WU Li-hong2，GU Wei-wang1. * Department of Laboratory Animal Center, Southern Medical University, Guangzhou, 510515, China. 2Stomatology Hospital of Guangzhou Medical University, Guangzhou, 510140, China. 【Abstract】 Objective To study its effect on rat nigrostriatal system and establish the rat model of Parkinsons disease and its evaluation by simulating human chronic exposure to paraquat through the digestive tract. Methods Rats were divided into high dose group (20 mg/kg paraquat, n = 16)，medium dose group(10 mg/kg paraquat, n = 16)，low dose group (5 mg/kg paraquat, n = 16) and the control group (normal saline, n = 16). Intragastric 4 months. We apply the behavioral detection system, the midbrain nigra and lung pathology observation, detecting the levels of striatum dopamine and related metabolites by HPLC etc. to analyze and evaluate it. Results After 4 months，compared with the control group, the performance of the low-dose group were normal，and some of rats in high dose group are unresponsive, stiff, tremulous. And the ability of learning and memory loss compared with the the control group (P = 0.001). Moreover, Compared with the control group，the substantia nigra pars compacta dopaminergic neurons was reduced significantly. DA in the striatum