三氧化二铁纳米磁流体对小鼠心肺组织的氧化损伤

Oxidative effects of Fe_2O_3 nano-magnetic fluid on mice hearts and lungs

背景:对于三氧化二铁纳米微粒氧化毒性研究尚显不足,尤其对心肺组织的损伤作用还未见相关报道,给磁流体在生物医学上的应用带来一定限制。目的:观察三氧化二铁纳米磁流体对小鼠心肺组织的氧化损伤毒性。设计、时间及地点:随机对照动物实验,于2008-03/05在兰州大学实验动物中心及相关实验室完成。材料:雄性二级BALB/C小鼠30只,随机分为对照组、低剂量组、高剂量组,10只/组。以L-谷氨酸作为表面活性剂的三氧化二铁水基纳米磁流体由兰州大学物理学院协助制备,三氧化二铁纳米微粒粒径20～50nm,磁流体呈棕红色悬浮液,pH值5.2,室温静置48h容器底未见明显沉淀。方法:3组均采用尾静脉注射方式,低剂量组给予5mg/kg三氧化二铁纳米磁流体,高剂量组给予20mg/kg三氧化二铁纳米磁流体,对照组给予等量生理盐水,1次/d,连续20d。染毒结束后,各组小鼠均眼眶取血0.5～1.0mL,检测血清中乳酸脱氢酶含量。取右肺称重(湿重),后置于60℃烘干至恒重(干重),以湿重/干重比值判断肺组织损伤水肿程度。取肺、心脏制备组织匀浆,测定过氧化物歧化酶、髓过氧化物酶活性及丙二醛含量。主要观察指标:血清中乳酸脱氢酶的含量及肺组织损伤水肿情况。肺、心脏组织氧化损伤指标的变化。结果:30只小鼠均进入结果分析。低剂量组及高剂量组血清中乳酸脱氢酶的含量、肺湿重/干重比值均明显高于对照组(t=39.161～39.312,t=9.929～10.622,P均<0.01),两剂量组间比较差异无显著性意义(t=5.987,t=0.977,P>0.05)。低剂量组及高剂量组的肺组织过氧化物歧化酶活性降低,髓过氧化物酶活性及丙二醛含量升高(P<0.01),且呈剂量-效应关系(P<0.01)。心肌氧化损伤的酶学指标低剂量组均无明显变化,但高剂量组过氧化物歧化酶活性降低,髓过氧化物酶活性及丙二醛含量升高(P<0.05)。结论:三氧化二铁纳米磁流体可在机体肺组织内产生大量自由基造成较为严重的肺部损伤,且呈剂量依赖性,对心脏的氧化损伤比较轻微。

BACKGROUND： The research about the oxidative toxicity of Fe2O3 nano-magnetic fluid is absent, and there is no report of the cardiopulmonary injury, thus the application of magnetic fluid on the field of biomedicine has been restricted. OBJECTIVE： To investigate the oxidative toxicity of Fe2O3 nano-magnetic fluid in hearts and lungs in mice. DESIGN, TIME AND SETTING： Randomized control animal experiments were performed in the Experimental Animal Center and Laboratory of Lanzhou University from March to May in 2008. MATERIALS： Thirty male BALB/C mice were randomly divided into control group, low dose group and high dose group, with 10 animals in each group. Using L-glutamic acid as surfactant, Fe203 nano-magnetic fluid was prepared in College of Physical Science, Lanzhou University. Fe2O3 nano-particle diameter was 20-50 nm, and Fe2O3 nano-magnetic fluid was suspension fluid colored as brownish red at pH value 5.2. No precipitation was found after staying for 48 hours at room temperature. METHODS： Mice were processed into different treatments through intravenous injections in tail, with 5 mg/kg Fe2O3 nano-magnetic fluid in low dose group, 20 mg/kg Fe2O3 nano-magnetic fluid in high dose group, and equal dose of saline in control group. The injection was daily conducted for 20 days successively. Orbital blood was sampled 0.5-1.0 mL to detect the content of lactic dehydrogenase in blood serum. Right lung was weighed in wet base and then dried 60 ℃ （dry weight）, the ratio of wet weight/dry weight was taken as a criterion of lung edema. Superoxide dismutase, malonaldehyde and myeloperoxidase in tissue homogenate of hearts and lungs were determined. MAIN OUTCOME MEASURES： Content of lactic dehydrogenase in blood serum and severity of lung edema were assayed. Changes of oxidative injury indexes in hearts and lungs were observed. RESULTS： Thirty mice were all involved in the result analysis. After the treatment, the lactic dehydrogenase in blood serum and the ratio of wet weight/dry weight increased in the low dose group and the high dose group compared to the control group （t=39.161-39.312, t=9.929-10.622, P 〈 0.01）; There was no significant differences between two dose groups （t=-5.987, t=0.977, P 〉 0.05）. The malonaldehyde and myeloperoxidase also increased in hearts and lungs, and the activity of superoxide dismutase decreased in low dose group and high dose group （P 〈 0.01）. These regulation effects were dose dependent （P 〈 0.01）. The enzymology changes of cardiac muscle oxidative injury were not significant in the low dose group （P 〉 0.05）. CONCLUSION： The Fe2O3 nano-magnetic fluid can produce excessive free radicals and thus cause obviously oxidative damages in lungs at a dose-dependent manner. Few affection is detectable in hearts.