LIPOSOME-ENTRAPPED SUPEROXIDE-DISMUTASE REDUCES CEREBRAL INFARCTION IN CEREBRAL-ISCHEMIA IN RATS

LIPOSOME-ENTRAPPED SUPEROXIDE-DISMUTASE REDUCES CEREBRAL INFARCTION IN CEREBRAL-ISCHEMIA IN RATS
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DOI:
10.1161/01.str.21.9.1312
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发表时间:
1990-09-01
期刊:
影响因子:
8.3
通讯作者:
CHAN, PH
CHAN, PH
中科院分区:
医学1区
文献类型:
--
作者:
IMAIZUMI, S;WOOLWORTH, V;CHAN, PH

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本实验采用102只大鼠局灶性脑缺血模型,以脂质体包埋的铜锌超氧化物歧化酶(CuZn-SOD)为载体,研究了超氧化物自由基在缺血性脑损伤发病中的作用。静脉推注25,000单位的脂质体包埋的CuZn-超氧化物歧化酶升高超氧化物歧化酶的活性在血液和脑1,2,8和24小时后,以及在缺血半球和对侧皮质。通过2,3,5-三苯基四氮唑氯化物对线粒体脱氢酶活性染色的缺乏,确定了右侧大脑中动脉和双侧颈总动脉闭塞后24小时,通过脂质体包埋的CuZn-超氧化物歧化酶治疗,前、中、后脑切片的梗死面积分别减少了33%、25%和18%。我们的数据表明,超氧化物自由基是重要的决定因素,梗死面积局灶性脑缺血和脂质体包埋铜锌超氧化物歧化酶可能有药理学价值的治疗局灶性脑缺血损伤。
We studied the role of superoxide radicals in the pathogenesis of ischemic brain injury using a model of focal cerebral ischemia in 102 rats and liposome-entrapped CuZn-superoxide dismutase, which can penetrate the blood-brain barrier and cell membranes efficiently. The bolus intravenous administration of 25,000 units of liposome-entrapped CuZn-superoxide dismutase elevated superoxide dismutase activities in the blood and brain 1, 2, 8, and 24 hours later as well as in the ischemic hemisphere and contralateral cortex. Determined 24 hours after right middle cerebral and bilateral common carotid artery occlusion by the lack of staining for mitochondrial dehydrogenase activity with 2,3,5-triphenyltetrazolium chloride, infarct sizes were reduced by 33%, 25%, and 18% in the anterior, middle, and posterior brain slices, respectively, by treatment with liposome-entrapped CuZn-superoxide dismutase. Our data demonstrate that superoxide radicals are important determinants of infarct size following focal cerebral ischemia and that liposome-entrapped CuZn-superoxide dismutase may have pharmacologic value for the treatment of focal cerebral ischemic injury.