摘要
目的：观察１甲基，４苯基１，２，３ ，６四氢吡啶（ ＭＰＴＰ） 和多巴胺对大鼠脑线粒体损伤作用。方法：大鼠脑线粒体与ＭＰＴＰ和多巴胺温孵后测定膜流动性、膜电位、线粒体肿胀、总ＡＴＰ酶、呼吸链复合酶活性及线粒体Ｈ２Ｏ２ ，Ｏ·２ 和丙二醛（ＭＤＡ）含量。结果：二者可降低线粒体膜流动性，ＭＰＴＰ损伤线粒体膜电位，对线粒体肿胀、总ＡＴＰ酶活性无影响；多巴胺不改变膜电位，却抑制总ＡＴＰ酶活性，导致线粒体肿胀。二者均增加线粒体中ＭＤＡ 含量。多巴胺使Ｈ２Ｏ２ 和Ｏ·２ 生成增加，ＭＰＴＰ仅增加Ｈ２Ｏ２ 生成。多巴胺抑制呼吸链复合酶活性，ＭＰＴＰ略有激活作用。结论：ＭＰＴＰ与多巴胺损伤线粒体作用的不同， 可能与通过不同途径刺激氧自由基生成有关。
AIM: To compare the toxic action of n methyl 4 phenyl 1,2,3,6 tetrahydro pyridine (MPTP) and dopamine on rat brain mitochondria. METHODS: After coincubation of MPTP or dopamine with isolated rat brain mitochondria, the membrane fluidity, membrane potential, mitochondrial swelling, the activity of total ATPase and mitochondrial respiratory chain as well as the levels of H 2O 2, O · 2 and malondialdehyde (MDA) were measured. RESULTS: Both MPTP and dopamine (1×10 -5 ～1×10 -3 mol·L -1 ) were shown to decrease mitochondrial membrane fluidity. MPTP decreased the mitochondrial membrane potential but did not induce swelling of mitochondria and decrease of total ATPase activity in mitochonria. Dopamine inhibited total ATPase activity and induced mitochondrial swelling but showed little effect on the membrane potential. Both compounds increased the MDA level. Dopamine enhanced both H 2O 2 and O · 2 generation in the mitochondria. MPTP only increased H 2O 2 generation. Dopamine significantly inhibited the respiratory chain activity. MPTP showed slight stimulating effect on respiratory chain activity. CONCLUSION: MPTP itself exhibited toxic action on rat brain mitochondria. Some of its effects were different from those of dopamine. The toxic effect of both compounds was related to the increment in production of reactive oxygen species through different pathways.
出处
《药学学报》
CAS
CSCD
北大核心
2000年第1期11-17,共7页
Acta Pharmaceutica Sinica
关键词
震颤性麻痹
MPTP
多巴胺
线粒体损伤
MPTP
dopamine
mitochondrial membrane potential
total ATPase
mitochondrial membrane fluidity
mitochondrial respiratory chain activity
reactive oxygen species
