小诺霉素与庆大霉素在小鼠钵内的时间毒性比较

COMPARISON OF CIRCADIAN RHYTHM OF TOXICITY BETWEEN MICRONOMICIN AND GENTAMICIN IN MICE

本实验在小鼠体内研究了小诺霉素与庆大霉素的急性毒性以及毒性与用药时间的依赖关系。以序贯法测得小诺霉素和庆大霉素在１３：００～１５：００腹腔注射后的ＬＤ（５０）分别为５１９．３４和２９４．９２ｍｇ／ｋｇ。再以此剂量利用时间生物学方法研究毒性与用药时间的依赖关系。取８０只昆明种雄性小鼠，体重１７～２４克，区组随机分组。在自然光线条件下的不同时间分别腹腔注射两药的ＬＤ（５０）剂量。各组动物用药时间为：０１：００、０７：００、１３：００和１９：００．观察并记录各组动物１小时内的死亡率。结果表明，小诺霉素和庆大霉素在１３：００时用药死亡率最高，均为４０％。小诺霉素在０７：００时死亡率最低而庆大霉素在０１：００时最低，分别为０％和１０％。不同时间用药的死亡率有显著性差异（Ｐ＜０．０５）。将上述数据以平均余弦拟合得最佳曲线方程，小诺霉素为Ｙ＝０，２２５０＋０．１５８１ｃｏｓ（１５°／ｈ．ｔ－２１３．０°）；庆大霉素为Ｙ＝０．１３７５＋０．１４８９ｃｏｓ（１５°／ｈ．ｔ－１９２．８°）。曲线表明小诺霉素和庆大霉素最高死亡率发生时间分别为１２：５１和１４：１４。上述实验结果说明：（１）小诺霉素的ＬＤ（５０）高于庆大霉素７６．?

The acute toxicity and toxicity-tirnf3 dependent relations-hip of Micronomicin(MIN)and Gentamicin(GEN)were investigated in mice.The LD(5)。of MIN and GEN were 519.34 and 294.92mg/kg determined inmice with sequentlal analysis after intraneritoneal administration within13:00～15:00.Male Kun-Ming mice(n =160, weight17～24g)were housed,ten to a cage in nature light phase and dark phase during May, with fr-ee access to food and water for 2 weeks befor experiment,80 mice weregiven intraperitoneally a single of MIN 519.34mg/kg,another 80mice were 294.92mg/kg of GEN at 01:00,07:00, 13:00, and 19:00 respectively. Theresults showed that the highest mortality (40%)of MIN and GEN presentedat 13:00;the lowest morlity of MIN(0%)and GEN (10%)at 07:00 and 01:00 respectively,The mortalities at different dosing times of day had sign-ificant variations.The curves xvere fitted with mean cosinor analysi;me-thod,The function of MIN xyas Y =0.1375+ 0.1489cos(15°/-192.8°) andGEN was Y=0.2250 +0.1581cos(15°/ht-213.6°),The highest mortality ofMIN was at 12: 51, GEN was at 14: 14,calculated from the functions.Theresults suggested that the LD(50) of MIN was higher 77.10% than that of GEN and toxlcity ofMIN was proved lower than that of GEN,The to-xicity of MIN and GEN depcnded on the dosing time of day with high-est toxicity during light phase and lowest during dark phase,In order to avolid or reduce the toxicity of MIN and CEN the dosage must be redesigned depending on the time of administration in clinical therapy.