摘要
目的评价SPIO标记的c-erbB2反义寡脱氧核苷酸探针对小鼠的急性毒性,为进一步将该探针用于活体MR基因成像与靶向基因治疗奠定基础。方法60只清洁级昆明种小鼠分为口服灌胃、静脉注射、腹腔注射3组,采用最大给药量法,口服灌胃:总剂量为2 104.8 mg/kg,给药容积40 ml/kg;静脉注射:总剂量为438.5 mg/kg,给药容积25 ml/kg;腹腔注射:总剂量为1 578.6 mg/kg,给药容积30 ml/kg;各组还另设20只小鼠按相应方式给予等量生理盐水作为对照。所有实验小鼠均在25℃室温下连续饲养14 d,观察并记录饲养期间小鼠的一般情况、主要脏器的病理学、血常规、凝血指标和血清主要生化指标改变。结果在观察期间,各组小鼠均未出现死亡,仅个别出现食欲下降、饮水量增多、腹泻、嗜睡、活动增加等,但均在3 d内恢复正常。脏器系数无统计学差异,肝、脾、肾、心、肺、骨髓、生殖器等主要脏器颜色、形态未见明显异常改变,HE染色切片肝、脾、肾、心、肺、生殖器等细胞和Wright染色的骨髓细胞均无水肿、变性、坏死等改变,普鲁士蓝染色仅见肝、脾内分布少许蓝色铁颗粒。各组血常规、凝血指标及生化指标无统计学差异。结论SPIO标记的c-erbB2反义寡脱氧核苷酸探针对小鼠无急性毒性。
Objective To investigate the acute toxicity in mice of an antisense oligodeoxynucleotide （ASODN） probes of oncogene c-erbB2 labeled by superparamagnetic iron oxide （SPIO） nanoparticle in order to make it be a target contrast agent for magnetic resonance （MR） imaging and targeting gene therapy. Methods Totally 60 health clean-grade Kunming mice were randomly and equally divided into oral administration, intravenous injection and intraperitoneal injection groups. All mice received the maximum dose although through different routes. The oral administration was given with a total dose of 2 104. 8 mg,/kg and a volume of 40 ml/kg, intravenous with a total dose of 438.5 mg/kg and a volume of 25 ml/kg, and intraperitoneal injection with a total dose of 1 578.6 mg/kg and a volume of 30 ml/kg respectively. Another 60 mice who received same dose of normal saline through same route served as the control group. All experimental mice were feed in 25 ℃ for 14 d. Their general condition, blood routine examination, coagulation indexes, main biochemical indexes and the pathological morphology of main viscera were tested and measured. Results During the observation period, there was no death in all mice, and only a few had appetite loss and increased water drinking, diarrhea, sleepiness, and more active, but all abnormalities disappeared in 3 d. There was no abnormality in gross observation and morphology of the liver, spleen, kidneys, heart, lungs, bone marrow and genitals. All cells of the liver, spleen, kidneys, heart, lungs, bone marrow and genitals had no edema, degeneration and necrosis either in HE or in Wright staining. There was no significant difference in the blood routine examination, coagulation indexes and biochemical indexes in experimental groups and control group. Conclusion SPIO labeled c-erbB2 ASODN probe has no acute toxicity to mice, and belongs to nontoxic compound.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2009年第5期398-401,共4页
Journal of Third Military Medical University
基金
国家自然科学基金(30070230)
重庆市自然科学基金(CSTC2008BB5209)
重庆市卫生局医学科研项目(062025)
重庆医科大学优秀博士基金(2006-182)~~
关键词
反义寡脱氧核苷酸
钠米粒子
超顺磁性氧化铁
毒理实验
antisense oligodeoxynucleotide
nanoparticles
superparamagnetic iron oxide
toxicity test
