王群林 李岩 许聪 卞伟华 张小华

摘要 [目的]采用长期纳米氧化锌腹腔内注射，初步测定纳米氧化锌颗粒对小鼠一般状态、肺及炎症介质的慢性影响。[方法] 取25 g左右健康小鼠22只，雌雄各半，随机分为空白对照组和试验组，每组11只。试验组小鼠给予腹腔注射83 mg/ml纳米氧化锌悬浊液各0.15 ml，连续注射7 d，对照注射等量生理盐水，注射药物结束3 d后观察小鼠一般状态并取材，肺叶称重测定湿干比（W/D），采用HE染色在光学显微镜下观察肺组织形态。采用ELISA法检测支气管肺泡灌洗液及血清中细胞间粘附分子1（ICAM1）和肿瘤坏死因子α（TNFα）含量。 [结果] 与对照组小鼠相比，试验组小鼠死亡率增加，平均体重明显减轻，肺的湿干比增高；血清及灌洗液中炎症因子TNFα及ICAM1 含量显著升高，存在显著性差异（P<0.05）；显微镜下可见肺组织有损伤。 [结论] 长期纳米氧化锌腹腔注射可对小鼠肺产生慢性不良影响。

关键词 纳米氧化锌；ICAM1；TNFα

中图分类号 S181；R994.6 文献标识码

A 文章编号 0517-6611（2014）31-10976-03

Chronic Effects of Nano Zinc Oxide in Mice

WANG Qunlin1， LI Yan2， XU Cong3， ZHANG Xiaohua3* et al （1. Department of Clinical Medicine， Binzhou Medical college， Yantai 264003；2.Respiratory Department，Affiliated Hospital of Binzhou Medical College，Binzhou，Shandong 256603；3.College of Pharmacy，Binzhou Medical College，Yantai，Shandong 264003）

Abstract [Objective] By longterm intraperitoneal injection of nanozinc oxide， preliminary determine chronic effects of nanozinc oxide particles on the general state of the mice， changes of liver and lung， and inflammatory mediators. [Method] Taking 22 healthy mice weighed about 25 g which were randomly divided into two groups， control group and the experimental group， 11 mice per group. The mice in experimental group were intraperitoneally injected nanozinc oxide suspension（0.83 mg / ml， 0.15ml） for 7 days， and the mice in control group were disposed of saline injection. 3 days after the end of injection， the general state of the mice was observed and specimens were drawn， lung weighing measured W/D. ELISA was used to test the content of intercellular adhesion molecule 1 （ICAM1） and tumor necrosis factorα （TNFα） in the bronchoalveolar lavage fluid and serum. Liver and lung tissue was obtained by means of anatomy and then stained with HE， morphology was observed under the microscope. [Result] Compared with the mice in control group， mice in the experimental group had increased mortality， significantly reduced average， weight W/D significantly increased； inflammatory cytokine TNFα and ICAM1 content in serum and lavage fluid were significantly increased， and the results are statistically significant （P<0.05）； liver and lung tissue damage could be visible in varying degrees under the optical microscope. [Conclusion] Longterm intraperitoneal injection of nanozinc oxide can produce chronic adverse effects on mice.

Key words Nano Zinc Oxide； ICAM1； TNFα

纳米氧化锌为一种新型无机多功能材料，是粒径介于1～100 nm的金属氧化物微粒^[1]。由于纳米氧化锌具有特殊优异的性能^[2]，使其在许多研究领域具有重要应用价值和广阔應用前景。目前，纳米氧化锌已被广泛应用于纺织^[3]、化妆品^[4]和医药等领域，不可避免地进入自然环境和生命体中^[5-6]，但其安全性一直广受争议。研究表明，纳米材料对人类身体健康和周围生态系统可能造成潜在危害，随着纳米毒理学的兴起和发展，纳米氧化锌的生物安全性被相关领域学者关注^[7]。笔者利用小鼠腹腔注射纳米氧化锌，通过观察小鼠一般状况（存活率、体重）和肺湿干质量比，观察小鼠肺组织形态学改变，检测支气管肺泡灌洗液及血清中ICAM1和TNFα含量变化，以探索纳米氧化锌对小鼠肺毒性的影响。……