Effects of adenosine receptor antagonists on the in vivo LPS-induced inflammation model of Parkinson's disease.
Effects of adenosine receptor antagonists on the in vivo LPS-induced inflammation model of Parkinson's disease.
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DOI：
10.1007/s12640-012-9372-1
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发表时间：
2013-07
影响因子：
3.7
通讯作者：
Gorska, Anna
中科院分区：
文献类型：
--
作者：
Golembiowska, Krystyna;Wardas, Jadwiga;Noworyta-Sokolowska, Karolina;Kaminska, Katarzyna;Gorska, Anna
本研究观察了非选择性腺苷A1/A2A受体拮抗剂咖啡因和选择性A2A受体拮抗剂KW6002对内毒素诱导的大鼠纹状体细胞外多巴胺(DA)、谷氨酸、腺苷、羟基自由基和A2A受体密度变化的影响。纹状体内注射脂多糖(10μg)后24 h，同侧胞外DA水平降低，腺苷、谷氨酸和羟基自由基水平升高。咖啡因(10和20 mg/kg ip)和KW6002(1.5和3 mg/kg ip)每天给药1次，连续给药6天，于注射前2小时和注射后4小时分别于第7天给药，逆转内毒素引起的细胞外DA、腺苷、谷氨酸和羟基自由基产生的变化。此外，咖啡因和KW6002可增加内毒素引起的纹状体A2A受体密度的降低。为探讨内毒素对多巴胺能神经元氧化损伤的影响，在双侧纹状体内注射内毒素(10μg)72h后，测定DA、DOPAC、HVA和羟基自由基的含量。脂多糖降低纹状体和黑质中DA、DOPAC和HVA的含量，而增加纹状体中羟基自由基的含量，但不增加黑质中的羟基自由基的含量。给予咖啡因(20 mg/kg)和KW60002(3 mg/kg)，每日1次，连续6天，在纹状体注射脂多糖前2小时和注射后4小时的第7天，使两个脑区DA及其代谢产物的含量恢复正常，并减轻内毒素引起的纹状体羟基自由基水平的增加。综上所述，我们的数据证实了咖啡因和KW6002在帕金森病炎症模型中的抗氧化作用。
The study shows effects of the nonselective adenosine A1/A2A receptor antagonist caffeine and the selective A2A receptor antagonist KW6002 on LPS-induced changes in the extracellular levels of dopamine (DA), glutamate, adenosine, hydroxyl radical, and A2A receptor density in the rat striatum. Intrastriatal LPS (10 μg) injection decreased extracellular level of DA and increased the level of adenosine, glutamate, and hydroxyl radical on the ipsilateral side 24 h after LPS administration. Caffeine (10 and 20 mg/kg i.p.) and KW6002 (1.5 and 3 mg/kg i.p.) given once daily for 6 days and on the 7th day 2 h before and 4 h after LPS injection reversed the LPS-induced changes in extracellular levels of DA, adenosine, glutamate, and hydroxyl radical production. Moreover, LPS-induced decrease in the striatal A2A receptor density was increased by caffeine and KW6002. In order to show the late LPS effect on oxidative damage of DA neurons, the contents of DA, DOPAC, HVA, and hydroxyl radical were determined 72 h after LPS (10 μg) administration into both striata. LPS decreased striatal and substantia nigra content of DA, DOPAC, and HVA while increased striatal but not nigral content of hydroxyl radical. Caffeine (20 mg/kg) and KW60002 (3 mg/kg) given once daily for 6 days and on the 7th day 2 h before and 4 h after intrastriatal injection of LPS normalized the content of DA and its metabolites in both brain regions as well as decreased LPS-induced increase in the striatal level of hydroxyl radical. In conclusion, our data demonstrated antioxidant effects of caffeine and KW6002 in the inflammatory model of PD.
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影响因子：
5.3
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