纳米二氧化硅致心肌线粒体损伤作用的研究

发布时间：2018-08-12 10:24

【摘要】：目的研究纳米二氧化硅对心肌细胞线粒体的毒性作用及机制。方法采用非暴露式气管内滴注的染毒方式对Balb/c小鼠进行3种浓度(7、21和35 mg/kg)粒径为40 nm左右的纳米二氧化硅暴露,另设对照组滴注等体积生理盐水。通过透射电子显微镜对小鼠心肌线粒体超微结构进行观察。通过对三磷酸腺苷(ATP)浓度的检测,评价纳米二氧化硅对心肌线粒体功能的影响。通过对心肌组织抗O~2~-·能力的检测,评价心肌细胞线粒体抗氧化能力。采用Western blot法对心肌组织中细胞色素c氧化酶1(COX1)和琥珀酸脱氢酶A(SDHA)蛋白表达水平进行检测,从而阐明纳米二氧化硅对心肌细胞线粒体生物合成的影响。结果与对照组相比,高剂量的纳米二氧化硅可导致线粒体结构的损伤,主要表现为线粒体肿胀、线粒体嵴排列紊乱甚至消失及线粒体融合。中、高剂量的纳米二氧化硅可导致心肌细胞线粒体功能下降。低、中剂量的纳米二氧化硅可引起心脏组织抗O~2~-·能力应激性升高,而高剂量的纳米二氧化硅则可导致心脏组织抗O~2~-·能力下降。中剂量的纳米二氧化硅可应激性诱导线粒体的生物合成,而高剂量的纳米二氧化硅则抑制线粒体的生物合成。结论高剂量的纳米二氧化硅可通过诱导线粒体内O~2~-·的产生、降低线粒体抗氧化能力,从而导致线粒体结构和功能的损伤,并抑制线粒体的生物合成。
[Abstract]:Objective to study the toxic effect and mechanism of nano silica on mitochondria of cardiomyocytes. Methods Balb/c mice were exposed to three concentrations (721 and 35 mg/kg) of nano-silica with the diameter of about 40 nm by intratracheal instillation, and the control group was given the same volume of normal saline. The ultrastructure of mouse myocardial mitochondria was observed by transmission electron microscope (TEM). The effects of nano silica on myocardial mitochondrial function were evaluated by detecting the concentration of adenosine triphosphate (ATP). The antioxidation ability of mitochondria was evaluated by detecting the anti-O 2 O 2 O 2 O 2 of myocardial tissue. The expression levels of cytochrome c oxidase 1 (COX1) and succinate dehydrogenase (A (SDHA) in myocardial tissue were detected by Western blot method to elucidate the effect of nano-silica on mitochondrial biosynthesis in cardiomyocytes. Results compared with the control group, high dose of nano-silica could lead to the damage of mitochondrial structure, such as swelling of mitochondria, disorder of mitochondrial cristae and even disappearance of mitochondrial fusion. High-dose nano-silica could decrease mitochondrial function in cardiomyocytes. Low and middle dose nano-silica could induce the increase of anti-O _ 2 ~ (2 +) -stress in heart tissue, while high dose of nano-silica could result in the decrease of anti-O _ (2) O _ (2) O _ (2) O _ (2) O _ (2) O _ (2) in cardiac tissue. Middle dose nano silica can induce mitochondrial biosynthesis by stress, while high dose nano silica can inhibit mitochondrial biosynthesis. Conclusion High-dose nano-silica can reduce the antioxidant capacity of mitochondria by inducing the production of O _ 2 ~ (2 +) in mitochondria, thus leading to the damage of mitochondrial structure and function and inhibiting the biosynthesis of mitochondria.
【作者单位】：首都医科大学公共卫生学院;
【基金】：国家自然科学基金资助项目(81402709,81573176) 北京市自然科学基金项目(7162021)
【分类号】：R114

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