三联吡啶锌配合物对小鼠的急性毒性研究  

Acute toxicity study of tripyridine-zinc complex in mice

作　　者：李霖珅 蒙淑玲 陈海秀 段晓鸽 罗家其 黄伟洋 江明生[1] 陈海兰[1,2,3] LI Lin-shen;MENG Shu-ling;CHEN Hai-xiu;DUAN Xiao-ge;LUO Jia-qi;HUANG Wei-yang;JIANG Ming-sheng;CHEN Hai-lan

机构地区：[1]广西大学动物科学技术学院,广西南宁530004 [2]广西壮族自治区兽用生物制品工程研究中心,广西南宁530004 [3]广西畜禽繁育与疾病防控重点实验室,广西南宁530004

出　　处：《饲料研究》2024年第21期74-79,共6页Feed Research

基　　金：大学生创新创业训练项目(项目编号:202310593452);国家自然科学基金(项目编号:32201095);巴马人才科技专项(项目编号:202100177)。

摘　　要：试验以昆明小鼠为研究对象,对三联吡啶锌配合物(LB-ZnI_(2))进行急性毒性试验研究。试验采用剂量递减法确定LB-ZnI_(2)对昆明小鼠的绝对致死剂量(LD_(100))和最大耐受剂量(LD_(0)),采用寇氏法设计动物分组方案及给药剂量,观察小鼠死亡情况、临床表现、重要脏器病理变化。结果显示,对昆明小鼠腹腔注射LB-ZnI_(2)的半数致死量(LD_(50))及其95%可信限分别为66.0 mg/kg·bw和53.8~80.9 mg/kg·bw。当药物剂量小于等于22 mg/kg·bw时,给药小鼠未出现死亡,且主要脏器形态、颜色和组织切片与正常对照组无显著差异;而当给药剂量大于33 mg/kg·bw时,小鼠开始出现死亡,死亡数量随着剂量增大而增加,且小鼠的肺脏出现淤血斑,脾脏出现萎缩,组织学观察发现脾脏中淋巴细胞坏死减少,脾小体萎缩,肺脏中肺泡上皮细胞脱落,肺间质增宽,大量炎性细胞浸润,同时充满大量红细胞,且这些变化与剂量呈正相关。研究表明,根据《兽药研究技术指导原则》(2006—2011年版)中化学物质的急性毒性剂量分级,可将LB-ZnI_(2)判定为中等毒化学物,在后续慢性毒性和药效学研究中的药物剂量应低于22 mg/kg·bw。The experiment used Kunming mice as a vehicle to conduct an acute toxicity study on the tripyridine-zinc complex(LB-ZnI_(2)).The absolute lethal dose(LD_(100))and the maximum tolerable dose(LD_(0))of LB-ZnI_(2) to Kunming mice were firstly determined by the dose declining method.Coriolis method was then used to design the animal grouping method and respective dosage.The death,clinical manifestations and pathological changes of important organs of mice were recorded during the experiment period.The results showed that,the median lethal dose(LD_(50))and 95%confidence limits of LB-ZnI_(2) provided by intraperitoneal injection were 66.0 mg/kg·bw and 53.8~80.9 mg/kg·bw.When the dosage was less than or equal to 22 mg/kg·bw,no death was happened,and there was no significant difference in the morphology,color and tissue section of the main organs between the treated mice and the normal control group.However,when the dosage was greater than 33 mg/kg·bw,the animal began to die and the number of deaths increased with the increase of drug dosage.In addition,the lung of mice were found to be congested with blood and the spleen were atrophied.Histological examination revealed decreased lymphocyte necrosis in the spleen,atrophy of the splenic corpuscle,shedding of alveolar epithelial cells in the lungs,widening of the lung interstitium,and infiltration of numerous inflammatory cells with abundant red blood cells.These changes were positively correlated with the applied dose.The study indicates that,according to the acute toxicity dosage classification of chemical substances in the Technical Guidelines for Veterinary Drug Research(2006—2011 edition),LB-ZnI_(2) can be judged as a moderately toxic chemical,and the drug dose should be lower than 22 mg/kg·bw in subsequent chronic toxicity and pharmacodynamics studies.

关 键 词：三联吡啶锌金属配合物 急性毒性试验 半数致死量 小鼠 

分 类 号：S816.7[农业科学—饲料科学]