摘要
目的研究长期低剂量皮下注射鱼藤酮制作Lew is大鼠帕金森病模型。方法Lew is大鼠随机分为正常对照组和模型组,以1.0 mg.kg-1.d-1的剂量皮下注射鱼藤酮,早晚2次注射,连续给药30 d,每周停药1 d。给药结束后,心脏灌注多聚甲醛固定,断头取脑,免疫组化和尼氏染色检测黑质(SN)多巴胺神经元损伤情况,并在共聚焦显微镜下观察α-synuc le in的聚集。结果模型组大鼠3只出现震颤。SN处酪氨酸羟化酶(TH)阳性细胞数也出现不同程度的减少,尼氏染色显示SN神经元减少,并伴有胶质细胞增生,黑质多巴胺能细胞胞浆内有-αsynuc le in阳性聚集体,模型成功率约为58%。结论长期皮下注射鱼藤酮(1.0 mg.kg-1.d-1)可复制大鼠帕金森病病理模型。
Aim To establish a rat model of Parkinsons disease by chronic subcutaneous injection of low-dose rotenone. Methotis Lewis rats were randomly divided into two groups: vehicletreated group and rotenone-treated group. Rotenone ( 1.0 mg · kg^-1 · d ^-1 ) was subcutaneously injected at 08 : 00 and 20 : 00 for 30 days with drug holidays every 7 days. Following 30 days of rotenone administration, neuronal loss in the substantia nigra ( SN ) was determined with tyrosine bydroxylase ( TH ) immunohistochemistry and Nissl staining. Aggregation of α-synuclein in SN neurons was observed with a laser cofocal microscopy. Resuit Three rotenone-treated rats showed resting tremor. The number of TH-positive neurons in SN significantly reduced ( P 〈 0. 05). Gliosis was observed in SN of rotenone-treated rats and α-synuclein-positive inculsion was found in the cytoplasm of SN neurons. The percentage of rotenone-treated rats with significant SN lesion was 58%. Conclusion Subcutaneous injection of low dose of rotenone ( 1.0 mg·kg^-1·d^-1 produces Parkinsoniasm in Lewis rats with low mortality and high successful rate.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2005年第10期1274-1277,共4页
Chinese Pharmacological Bulletin
基金
香港保健协会科研基金资助项目(No20030816)