Muralikrishnan D, Mohanakumar K P
Laboratory of Neurochemistry, Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, Calcutta.
FASEB J. 1998 Jul;12(10):905-12. doi: 10.1096/fasebj.12.10.905.
Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg i.p. twice, 16 h apart). This resulted in changes in motor performance and toxic insult of nigral neurons as evidenced by dopamine depletion in nucleus caudatus putamen. In vitro and in vivo treatment of MPTP caused the generation of hydroxyl radicals (.OH) as measured by a sensitive salicylate hydroxylation procedure. A dopamine agonist, bromocriptine (10 microM and 10 mg/kg i.p.), blocked .OH formation caused by MPTP in vitro (20 microM) and in vivo (30 mg/kg i.p.). An MPTP-induced increase in the activity of catalase and superoxide dismutase in substantia nigra on the seventh day was reduced by bromocriptine pretreatment. Bromocriptine blocked MPTP-induced behavioral dysfunction as well as glutathione and dopamine depletion, indicating its potent neuroprotective action. This study suggests that bromocriptine stimulates antioxidant mechanisms in the brain and acts as a free radical scavenger in addition to its action at dopamine receptors, thus indicating its strength as a valuable neuroprotectant.
小鼠用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP；30mg/kg腹腔注射，间隔16小时，共两次）处理。这导致运动性能改变以及黑质神经元受到毒性损伤，尾状核壳核中的多巴胺耗竭证明了这一点。通过灵敏的水杨酸羟化程序测量，MPTP的体外和体内处理均导致羟基自由基（·OH）的产生。多巴胺激动剂溴隐亭（10μM和10mg/kg腹腔注射）可阻断MPTP在体外（20μM）和体内（30mg/kg腹腔注射）引起的·OH形成。溴隐亭预处理可降低MPTP诱导的第七天黑质中过氧化氢酶和超氧化物歧化酶活性的增加。溴隐亭可阻断MPTP诱导的行为功能障碍以及谷胱甘肽和多巴胺耗竭，表明其具有强大的神经保护作用。本研究表明，溴隐亭除了作用于多巴胺受体外，还能刺激大脑中的抗氧化机制并作为自由基清除剂，从而表明其作为有价值的神经保护剂的优势。
