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地尔硫䓬对γ射线照射小鼠细胞遗传损伤和存活率的辐射防护作用。

Radioprotective effects of diltiazem on cytogenetic damage and survival in gamma ray exposed mice.

作者信息

Goel H C, Ganguly S K, Prasad J, Jain V

机构信息

Institute of Nuclear Medicine & Allied Sciences, Lucknow Marg, Delhi, India.

出版信息

Indian J Exp Biol. 1996 Dec;34(12):1194-200.

PMID:9246909
Abstract

Diltiazem, a calcium ion channel blocker, already in use in cardiovascular therapeutics, has been observed to protect against bone marrow damage (cytogenetic damage, cell death) and mortality in whole body irradiated mice. The micronuclei fraction in bone marrow cells of whole body irradiated (60Co gamma rays, 2.0 Gy) mice was reduced from 2.24 +/- 0.23% to about 0.74 +/- 0.33% by preirradiation administration (-20 min) of 110 mg/kg body wt. diltiazem (ip). Endogenous colony forming unit counts in spleen of mice administered 110 mg/kg body wt. (-20 min) of diltiazem before 10 Gy whole body irradiation were 6 times more than untreated irradiated controls. Pretreatment with diltiazem accelerated the recovery of radiation induced weight loss also. Diltiazem (110 mg/kg body wt, -20 min) enhanced 30 day survival to about 95% and 85% after lethal whole body absorbed dose of 9 and 10 Gy respectively and also mitigated radiation induced life- span shortening. Post-irradiation (10 Gy) administration of diltiazem (+20 to 30 min) enhanced survival from about 2 to 15% only but was highly significant (P < 0.001). Possible modes of radioprotective action of diltiazem have been discussed.

摘要

地尔硫䓬是一种钙离子通道阻滞剂,已用于心血管治疗,据观察,它可以保护受全身照射的小鼠免受骨髓损伤(细胞遗传学损伤、细胞死亡)并降低死亡率。对全身照射(60Coγ射线,2.0 Gy)的小鼠,在照射前(-20分钟)腹腔注射110毫克/千克体重的地尔硫䓬,可使骨髓细胞中的微核率从2.24±0.23%降至约0.74±0.33%。在10 Gy全身照射前给小鼠腹腔注射110毫克/千克体重(-20分钟)的地尔硫䓬,其脾脏中内源性集落形成单位的数量是未处理的照射对照组的6倍。地尔硫䓬预处理还加速了辐射引起的体重减轻的恢复。地尔硫䓬(110毫克/千克体重,-20分钟)分别在9 Gy和10 Gy的致死性全身吸收剂量后,使30天存活率提高到约95%和85%,并减轻了辐射引起的寿命缩短。照射后(10 Gy)给予地尔硫䓬(+20至30分钟)仅使存活率从约2%提高到15%,但具有高度显著性(P<0.001)。文中讨论了地尔硫䓬的可能辐射防护作用模式。

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