重组犬α干扰素急性毒性试验的研究.docVIP

重组犬α干扰素急性毒性试验的研究 　　摘要为观察小鼠体内重组犬α干扰素急性毒性反应,进行重组犬α干扰素临床安全用药试验。结果表明:在连续观察14 d内,各组小鼠外部表现及行为特征均正常,体温和体重的变化也在正常范围之内,内脏病理解剖无器官病变情况,血液生化指标检查;注射1.0×106IU/只雌性小鼠ALT为(85.2±5.2)U/L,较正常对照组高,其他各组生化指标与对照组相比无显著性差异(P0.05)。可见,该试验设定的最高剂量1.0×106IU/只及其以下剂量对小白鼠均无明显毒性作用,在临床上应用该重组犬α干扰素是安全的。 　　关键词重组犬α干扰素;急性毒性实验;小鼠 　　中图分类号S859.8文献标识码A文章编号 1007-5739(2010)14-0286-02 　　 　　ExperimertalResearchonActuteToxicityofMicewithRecombinantCanineIFN-α 　　LUO Chang-min 1ZHAO Jun 2TANG Ren-shu 2LI Jing-pei 2HU Yong 2WANG Yan-lai 2WANG Ming-li 2 * 　　(1 Immunology Teaching and Research Section,Anhui Medical University,Hefei Anhui 230032; 2 Microbiology Teaching and Resarch Section,Anhui Medical Umiversity) 　　AbstractAcute toxicity in mice with recombinant canine IFN-α in vivo was studied in order to provide a basis for clinical drug safety. The results showed that:during 14 days of continuous observations,the external performance and behavioral characteristics of mice in each group were normal,the changes of body temperature and weight were within normal range,pathological anatomy of internal organs had no organ lesions,bloodbiochemical examination; ALT in female mice after being injected by 1.0×106 IU every mouse was(85.2±5.2)U/L,more than the normal control group,other groups had no significant differences from the normal control group(P0.05). This experiment set the maximum dose 1.0×106 IU for a mouse and the below dose had no apparent toxic effects on mouse. It was prompted that the application of recombinant canine IFN-α in the clinical was safe. 　　Key wordsrecombinant canine IFN-α;acute toxicity;mouse 　　 　　近年来,养犬业在中国发展迅速,犬作为伴侣动物已成为人们生活的一部分,但犬细小病毒、犬瘟热等病毒病严重危害着犬类的健康与生存,同时犬所携带的一些人兽共患病原体也严重危害人类的健康。在现代社会犬病毒病的预防和治疗显得尤为重要。干扰素(interferon,IFN)是病毒感染诱导机体产生的一种具有广谱抗病毒、抗肿瘤、免疫调节作用的蛋白质,主要通过抑制病毒基因转录和降解病毒RNA来抑制病毒的生长繁殖及发挥抗肿瘤的活性。干扰素对动物病毒性疾病具有较好的防治效果[1-3]。按照干扰素的产生细胞、生化特征及在机体免疫方面所发挥的作用不同,分为α、β、γ3类。α型干扰素在体内外能发挥广谱、高效抗病毒作用,其机制是抑制病毒蛋白质的合成,并能选择性地作用于受感染细胞,而对正常宿主细胞无作用或作用微弱,使用后无任何药物残留。最早应用于兽医临床的是白细胞干扰素(IFN)。但该种IFN在体内表达量低,需采