纳米二氧化钛对小鼠心肌细胞DNA的损伤及叔丁基对苯二酚的拮抗作用

发布时间：2018-06-27 22:26

本文选题：纳米二氧化钛 + 叔丁基对苯二酚　；参考：《复旦学报(医学版)》2015年03期

【摘要】：目的探讨纳米二氧化钛(nano-titanium dioxide,Nano-TiO2)对小鼠心肌细胞DNA的损伤作用,并进一步研究核因子NF-E2相关因子(nuclear factor erythroid 2-related factor 2,Nrf2)诱导剂叔丁基对苯二酚(tertbutylhydroquinone,tBHQ)是否可降低此种损伤。方法 30只ICR小鼠随机分为6组:对照组,Nano-TiO2低(0.5g/kg)、中(1g/kg)、高(2g/kg)剂量组,tBHQ组,tBHQ+Nano-TiO2组。Nano-TiO2灌胃给予,tBHQ腹腔注射,均1次/天,连续7天。末次染毒后24h处死小鼠,取新鲜心脏组织,胰酶消化法制备心肌细胞悬液,采用单细胞凝胶电泳技术检测心肌细胞DNA损伤程度。结果 (1)对照组心肌细胞核呈圆形荧光团,强度均匀,大小较一致,无明显拖尾。不同剂量Nano-TiO2染毒后,各组均存在不同数量的DNA受损心肌细胞,出现彗星拖尾现象,且其尾部的拖尾程度及荧光强度随Nano-TiO2剂量的增加而增强。经CASP软件分析,低、中、高剂量Nano-TiO2组尾部DNA含量(tail DNA percent,TD)分别为28.45±1.70、35.08±0.81、39.94±4.46,明显高于对照组(23.96±2.59),差异有统计学意义(P0.01),并有良好的剂量-效应关系(r=0.9947)。低、中、高剂量Nano-TiO2组彗星尾矩(olive tail moment,OTM)较对照组均有明显增加且差异有统计学意义(P0.05),并有良好的剂量-效应关系(r=0.9886)。(2)tBHQ组心肌细胞细胞核呈圆形,无拖尾;Nano-TiO2中剂量(1g/kg)组细胞拖尾明显,但给予tBHQ可明显降低Nano-TiO2所致的细胞核拖尾程度;与Nano-TiO2组相比,tBHQ+Nano-TiO2组两项指标TD及OTM均明显降低,且差异有统计学意义(P0.05)。结论 Nano-TiO2可剂量依赖性地引起心肌细胞DNA损伤,而Nrf2诱导剂tBHQ可拮抗Nano-TiO2所致心肌细胞DNA损伤。
[Abstract]:Objective to investigate the damage of nano-titanium dioxide-nano-TiO _ 2 on cardiomyocytes in mice, and to further study whether tertbutylhydroquinone tBHQ, an inducer of nuclear factor NF-E2 related factor (nuclear factor erythroid 2-related factor _ 2nrf2, can reduce the damage. Methods Thirty ICR-mice were randomly divided into 6 groups: control group with low (0.5g/kg), moderate (1g/kg) and high dose (2g/kg) groups were given intraperitoneal injection of tBHQ Nano-TiO _ 2. Nano-TiO _ 2 was administered intraperitoneally once a day for 7 days. The mice were killed 24 hours after the last exposure. The fresh heart tissue was taken and the myocardial cell suspension was prepared by trypsin digestion. The degree of DNA damage in cardiomyocytes was detected by single cell gel electrophoresis (SCGE). Results (1) the nuclei of the control group were round fluorescent clusters with uniform intensity, uniform size and no obvious tail dragging. After different doses of Nano-TiO _ 2, there were different amounts of DNA damaged cardiomyocytes in each group, and the tail trailing degree and fluorescence intensity of the tail increased with the increase of Nano-TiO _ 2 dose. The results of CASP software showed that the tail DNA concentration (TD) in the low, middle and high dose Nano-TiO _ 2 group was 28.45 卤1.70 ~ 35.08 卤0.81 卤39.94 卤4.46, which was significantly higher than that in the control group (23.96 卤2.59). The difference was statistically significant (P0.01) and had a good dose-effect relationship (r _ (0.9947). In the low, middle and high dose Nano-TiO _ 2 groups, the comet tail moment (olive tail momentum) increased significantly compared with the control group (P0.05), and there was a good dose-response relationship (r _ (0.9886). (_ (2) in the myocardial nuclei of the tBHQ group, and the tail of the cells in the non-trailing Nano-TiO _ (2) medium dose (1g/kg) group was obvious. Compared with Nano-TiO2 group, the TD and OTM of tBHQ Nano-TiO2 group were significantly lower than those of Nano-TiO2 group, and the difference was statistically significant (P0.05). Conclusion Nano-TiO _ 2 can induce DNA damage in cardiomyocytes in a dose-dependent manner, while NRF _ 2 inducer tBHQ can antagonize the DNA damage induced by Nano-TiO _ 2.
【作者单位】：河北医科大学公共卫生学院;河北医科大学公共卫生学院卫生毒理学教研室;
【基金】：国家自然科学基金(81102151,81473292) 河北省自然科学基金(H2013206292) 2014年国家级大学生创新创业训练计划项目(201410089015)~~
【分类号】：R114

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