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3种β受体阻滞剂对甲状腺功能亢进性肌肉脂质过氧化的不同作用。

Differential effects of 3 beta blockers on lipid peroxidation in hyperthyroid muscle.

作者信息

Asayama K, Hayashibe H, Dobashi K, Kato K

机构信息

Department of Pediatrics, Yamanashi Medical College, Japan.

出版信息

Endocrinol Jpn. 1990 Aug;37(4):471-8. doi: 10.1507/endocrj1954.37.471.

DOI:10.1507/endocrj1954.37.471
PMID:1707360
Abstract

To determine whether beta blockade protects against the acceleration of lipid peroxidation in hyperthyroid rat soleus (slow-oxidative) muscle, in vivo chronic (3 weeks) effects of 3 beta blockers with different ancillary properties on mitochondrial oxidative enzymes, antioxidant enzymes, and thiobarbituric acid-reactive substances were investigated. The rats were rendered hyperthyroid by the administration of thyroxine and treated simultaneously with either carteolol (a nonselective blocker with partial agonist activity; 30 mg/kg/day), atenolol (a beta 1-selective blocker; 50 mg/kg/day), or arotinolol (a nonselective blocker with weak alpha-blocking action; 50 mg/kg/day) over a 3 week period. Hyperthyroidism induced tachycardia, an increase in the mitochondrial oxidative enzymes, manganese (mitochondrial) superoxide dismutase and thiobarbituric acid-reactive substances, and a decrease in the other antioxidant enzymes. The tachycardia was alleviated completely by either atenolol or arotinolol, but partially by carteolol. Arotinolol, but neither carteolol nor atenolol, inhibited the increase in oxidative enzymes and thiobarbituric acid-reactive substances. The levels of antioxidant enzymes were minimally affected by the beta-blocker treatment. Beta 2-, and possibly alpha- as well, but not beta 1-, blockade suppressed mitochondrial hypermetabolism and protected against peroxidative injury in the hyperthyroid soleus muscle. Partial agonist activity was not beneficial.

摘要

为了确定β受体阻滞剂是否能防止甲状腺功能亢进大鼠比目鱼肌(慢氧化型)脂质过氧化加速,研究了三种具有不同辅助特性的β受体阻滞剂对线粒体氧化酶、抗氧化酶和硫代巴比妥酸反应性物质的体内慢性(3周)影响。通过给予甲状腺素使大鼠甲状腺功能亢进,并在3周内同时用卡替洛尔(一种具有部分激动剂活性的非选择性阻滞剂;30毫克/千克/天)、阿替洛尔(一种β1选择性阻滞剂;50毫克/千克/天)或阿罗洛尔(一种具有弱α阻断作用的非选择性阻滞剂;50毫克/千克/天)进行治疗。甲状腺功能亢进导致心动过速、线粒体氧化酶、锰(线粒体)超氧化物歧化酶和硫代巴比妥酸反应性物质增加,以及其他抗氧化酶减少。阿替洛尔或阿罗洛尔可完全缓解心动过速,而卡替洛尔只能部分缓解。阿罗洛尔可抑制氧化酶和硫代巴比妥酸反应性物质的增加,而卡替洛尔和阿替洛尔则不能。β受体阻滞剂治疗对抗氧化酶水平的影响最小。β2受体阻断,可能还有α受体阻断,但不是β1受体阻断,可抑制线粒体高代谢并防止甲状腺功能亢进比目鱼肌发生过氧化损伤。部分激动剂活性并无益处。

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