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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 pulmonary toxicity of nano-sized cerium oxide particles to rats and its ability to induce pulmonary fibrosis in rats. Methods Fifty male Sprague-Dawley rats were randomly divided into five groups: high-dose Nano-CeO2 (10 mg · kg-1, nano-high group), low-dose Nano CeO2 (2 mg · kg- 1, nano-low group), micro-cerium oxide high-dose group (10mg · kg-1, micro-high group), micro-cerium oxide low dose group (2mg · kg- (control group), each group of 10. Non-exposed endotracheal injection of each group were injected with the corresponding reagents, injected once every other day, a total of 25 times. After 50 days, the rats were sacrificed and the body weight, lung coefficient, hydroxyproline content and alveolar macrophage (AM) apoptosis rate were measured in all groups. Van-Gieson staining was used to observe the lung Tissue paraffin sections of pulmonary fibrosis. Results After tracheal injection of the corresponding agents for 50 days, there was no significant difference in body weight and lung coefficient between the two groups (P> 0.05). The content of hydroxyproline in nano-high group was significantly higher than that in control group and micro-high group (P <0.05). The apoptosis rate of nano-high group was significantly higher than that in control group (P <0.01) -high group was no significant difference (P> 0.05); Van-Gieson staining results showed that nano-cerium-induced lung fibrosis is more significant than the micron cerium oxide. Conclusion Cerium oxide has a certain role in inducing pulmonary fibrosis. There is a dose-response relationship between particle size and toxicity. The effect of cerium oxide on pulmonary fibrosis is stronger than that of micron-sized cerium oxide.