纳米氧化铈致大鼠肺纤维化作用的研究

Effects of Nano Cerium Oxide on Pulmonary Fibrosis in Rats

目的探讨纳米氧化铈颗粒对大鼠的肺毒性及其致大鼠肺纤维化的能力。方法将50只雄性SD大鼠按随机数字表法分为5组:纳米氧化铈高剂量组(10 mg·kg-1,nano-high组)、纳米氧化铈低剂量组(2 mg·kg-1,nano-low组)、微米氧化铈高剂量组(10mg·kg-1,micro-high组)、微米氧化铈低剂量组(2mg·kg-1,micro-low组)、生理盐水对照组(control组),每组10只。采用非暴露式气管内注射方式分别注射各组对应试剂,隔日注射1次,共25次。50d后处死大鼠,测定各组大鼠体质量、肺脏系数、肺组织羟脯氨酸含量、肺泡巨噬细胞(alveolar macrophage,AM)凋亡率,采用Van-Gieson染色观察各组大鼠肺组织石蜡切片肺纤维化情况。结果经气管注射相应试剂50d后,各组大鼠体质量、肺脏系数比较差异均无统计学意义(P>0.05)。nano-high组羟脯氨酸含量较control组、micro-high组均显著增加(P<0.05);nano-high组AM凋亡率与control组相比显著增加(P<0.01),而与micro-high组差异无统计学意义(P>0.05);Van-Gieson染色结果发现,纳米氧化铈所致肺组织纤维化较微米氧化铈更为显著。结论氧化铈有一定的致肺纤维化的作用,存在粒径大小和毒性剂量反应关系,纳米氧化铈的致肺纤维化作用强于微米氧化铈。

Objective To investigate the effects of nano cerium oxide on pulmonary toxicity and its ability to induce pulmonary fibrosis in rats.Methods A total of 50 male SD rats were randomly treated with high dose nano cerium oxide(10mg·kg^(-1),nano-high group),low dose nano cerium oxide(2mg·kg^(-1),nano-low group),high dose micro cerium oxide(10mg·kg^(-1),micro-high group),low dose micro cerium oxide(2 mg·kg^(-1),micro-low group)and normal saline(control group),with 10 rats in each group.Rats were administered 25 times by intratracheal instillation every other day.After treatment for 50 days,rats were sacrificed and the body weight,lung coefficient,hydroxyproline content and alveolar macrophage(AM)apoptosis were measured.Paraffinembedded lung tissue sections were stained with Van-Gieson to observe the pulmonary fibrosis.Results There were no significant differences in body weight and lung coefficient among the five groups(P>0.05).The content of hydroxyproline in nano-high group were significantly higher than control group and micro-high group(P<0.05),The apoptosis rate of AM in nano-high group was significantly higher than control group(P<0.01),The apoptosis rate of AM in nano-high group was no significant differences than micro-high group(P >0.05).Van-Gieson staining showed that nano cerium oxide induced more serious pulmonary fibrosis than micro cerium oxide.Conclusion Cerium oxide causes pulmonary fibrosis,and shows a dose-response relationship to particle size.Nano cerium oxide is superior to micro cerium oxide for inducing pulmonary fibrosis.