阿朴酯颗粒剂对小鼠肝肾组织毒性、血清炎性因子及体液免疫水平的影响  

Effects of Apo-ester granules on liver and kidney tissue toxicity,serum inflammatory factors and humoral immunity in mice

作　　者：王剑 廖书丹 杨剑 文正常[3] 金晓峰[4] 赵贵[4] 吕世明[1,2] WANG Jian;LIAO Shu-dan;YANG Jian;WEN Zheng-chang;JIN Xiao-feng;ZHAO Gui;LYU Shi-ming(College of Animal Science,Guizhou University,Guiyang 550025,China;Guizhou Key Laboratory of Animal Disease and Veterinary Public Health,Guiyang 550025,China;Guizhou Institute of Animal Husbandry and Veterinary Medicine,Guiyang 550005,China;Guizhou Provincial Veterinary Medicine Feed Supervision Office,Guiyang 550003,China)

机构地区：[1]贵州大学动物科学学院,贵阳550025 [2]贵州省动物疫病与兽医公共卫生重点实验室,贵阳550025 [3]贵州省畜牧兽医研究所,贵阳550005 [4]贵州省兽药饲料监察所,贵阳550003

出　　处：《南方农业学报》2022年第1期200-209,共10页Journal of Southern Agriculture

基　　金：国家自然科学基金项目(31760749);贵州省科技攻关计划项目(黔科合支撑〔2019〕2318号);贵州省科技计划项目(黔科合基础-ZK〔2022〕129号);贵州省普通高等学校青年科技人才成长项目(黔教合KY字〔2022〕151号)。

摘　　要：【目的】观察长期添加阿朴酯颗粒剂对昆明小鼠肝脏、肾脏组织结构与功能及其体液免疫水平的影响,系统评价其安全性,为阿朴酯在畜禽生产中的科学应用提供参考依据。【方法】通过急性毒性试验测定阿朴酯颗粒剂对昆明小鼠的半数致死量(LD_(50)),然后设50%LD_(50)(1.4 g/kg)和80%LD_(50)(2.2 g/kg)作剂量组,以等量生理盐水为空白对照。单次灌胃1.4 g/kg阿朴酯悬浊液后,于灌胃后第4、12、36和60 h及第7和14 d进行眼球采血,用于测定血常规指标;按1.4和2.2 g/kg的剂量分别连续灌胃阿朴酯悬浊液21 d后,分析小鼠体重增重、血清生化指标、尿常规指标及免疫指标的变化情况,并采集小鼠肝脏和肾脏制作石蜡切片进行组织学观察。【结果】阿朴酯颗粒剂对昆明小鼠的LD_(50)为2.74 g/kg,95%置信限为2.69~3.41 g/kg。依据WHO毒性分级标准,阿朴酯颗粒剂属低毒级物质。按1.4 g/kg的剂量单次灌胃阿朴酯悬浊液后,昆明小鼠血液中性粒细胞数量在灌胃后第4 h显著升高(P<0.05,下同),白细胞总数在灌胃后第12和36 h显著升高,淋巴细胞数量在灌胃后第4和12 h极显著升高(P<0.01,下同),红细胞总数和平均红细胞血红蛋白含量在灌胃后第36 h显著升高。以2.2 g/kg的剂量连续灌胃阿朴酯悬浊液21 d后,昆明小鼠的体重增重和平均日增重极显著降低,血清中的碱性磷酸酶活性和尿素含量极显著升高、而谷草转移酶活性和肌酐含量极显著降低;尿液中白细胞数量及蛋白、微白蛋白和酮体含量显著上升;肝脏黄染、淤血,肝索与肝窦紊乱不清,肝细胞碎裂溶解,发生肿胀或坏死;肾脏明显肿大、黄染,肾小体破损消亡,髓质部呈弥漫性出血;血清免疫细胞因子IL-1β、TNF-α和IL-10水平显著或极显著升高,而免疫球蛋白IgM和SIgA浓度显著下降。【结论】阿朴酯颗粒剂属低毒级物质,但高剂量使用可快速升高血细胞数量,破坏小鼠肝�【Objective】The effects of long-term addition of Apo-ester(APO)granules on the structure and function of liver,kidney and humoral immunity levels in Kunming mice were investigated,and its safety was systematically evalua-ted,which would provide a reference for the scientific application of APO in livestock and poultry production.【Method】The median lethal dose(LD_(50))of APO granules was measured by acute toxicity test on Kunming mice.Then,50%LD_(50)(1.4 g/kg)and 80%LD_(50)(2.2 g/kg)were set as dose groups and equal amount of saline was used as blank control.After a single gavage of 1.4 g/kg APO suspension,eye blood was collected on the 4^(th),12^(th),36^(th) and 60^(th) h and on the 7^(th) d and 14^(th) d after the gavage for the determination of blood routine indexes.After 21 d of continuous gavage of APO suspension at 1.4 and 2.2 g/kg,the weight gain,blood biochemical indexes,urinary indexes immune indexes of mice were analyzed.Besides,the liver and kidney were collected for histological observation in paraffin sections.【Result】The LD_(50) of APO granules on Kunming mice was 2.74 g/kg with the 95%confidence limit of 2.69-3.41 g/kg.According to the toxicity grading standard of WHO,APO granule was a low-toxicity substance.The blood neutrophils of Kunming mice increased significantly(P<0.05,the same below)at the 4^(th) h after single gavage of APO suspension at a dose of 1.4 g/kg.The total number of white blood cells was significantly increased at 12^(th) and 36^(th) h after gavage,and the number of lymphocytes was extremely significantly increased at 4^(th) and 12^(th) h after gavage(P<0.01,the same below).The total number of erythrocytes and the mean erythrocyte hemoglobin content increased significantly at 36^(th) h after gavage.The body weight gain and mean daily weight gain of Kunming mice were extremely significantly reduced after 21 d of continuous gavage of APO suspension at a dose of 2.2 g/kg.Serum alkaline phosphatase activity and urea content were extremely significantly increased,while tangr

关 键 词：阿朴酯颗粒剂 小鼠 肝肾毒性 血清炎性因子 体液免疫 

分 类 号：S816.74[农业科学—饲料科学]