本文選題：納米二氧化鈦 + 叔丁基對苯二酚��； 參考：《復(fù)旦學(xué)報(醫(yī)學(xué)版)》2015年03期

【摘要】：目的探討納米二氧化鈦(nano-titanium dioxide,Nano-TiO2)對小鼠心肌細(xì)胞DNA的損傷作用,并進(jìn)一步研究核因子NF-E2相關(guān)因子(nuclear factor erythroid 2-related factor 2,Nrf2)誘導(dǎo)劑叔丁基對苯二酚(tertbutylhydroquinone,tBHQ)是否可降低此種損傷。方法 30只ICR小鼠隨機分為6組:對照組,Nano-TiO2低(0.5g/kg)、中(1g/kg)、高(2g/kg)劑量組,tBHQ組,tBHQ+Nano-TiO2組。Nano-TiO2灌胃給予,tBHQ腹腔注射,均1次/天,連續(xù)7天。末次染毒后24h處死小鼠,取新鮮心臟組織,胰酶消化法制備心肌細(xì)胞懸液,采用單細(xì)胞凝膠電泳技術(shù)檢測心肌細(xì)胞DNA損傷程度。結(jié)果 (1)對照組心肌細(xì)胞核呈圓形熒光團,強度均勻,大小較一致,無明顯拖尾。不同劑量Nano-TiO2染毒后,各組均存在不同數(shù)量的DNA受損心肌細(xì)胞,出現(xiàn)彗星拖尾現(xiàn)象,且其尾部的拖尾程度及熒光強度隨Nano-TiO2劑量的增加而增強。經(jīng)CASP軟件分析,低、中、高劑量Nano-TiO2組尾部DNA含量(tail DNA percent,TD)分別為28.45±1.70、35.08±0.81、39.94±4.46,明顯高于對照組(23.96±2.59),差異有統(tǒng)計學(xué)意義(P0.01),并有良好的劑量-效應(yīng)關(guān)系(r=0.9947)。低、中、高劑量Nano-TiO2組彗星尾矩(olive tail moment,OTM)較對照組均有明顯增加且差異有統(tǒng)計學(xué)意義(P0.05),并有良好的劑量-效應(yīng)關(guān)系(r=0.9886)。(2)tBHQ組心肌細(xì)胞細(xì)胞核呈圓形,無拖尾;Nano-TiO2中劑量(1g/kg)組細(xì)胞拖尾明顯,但給予tBHQ可明顯降低Nano-TiO2所致的細(xì)胞核拖尾程度;與Nano-TiO2組相比,tBHQ+Nano-TiO2組兩項指標(biāo)TD及OTM均明顯降低,且差異有統(tǒng)計學(xué)意義(P0.05)。結(jié)論 Nano-TiO2可劑量依賴性地引起心肌細(xì)胞DNA損傷,而Nrf2誘導(dǎo)劑tBHQ可拮抗Nano-TiO2所致心肌細(xì)胞DNA損傷。
[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 鹵1.70 ~ 35.08 鹵0.81 鹵39.94 鹵4.46, which was significantly higher than that in the control group (23.96 鹵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.
【作者單位】： 河北醫(yī)科大學(xué)公共衛(wèi)生學(xué)院;河北醫(yī)科大學(xué)公共衛(wèi)生學(xué)院衛(wèi)生毒理學(xué)教研室;
【基金】：國家自然科學(xué)基金(81102151,81473292) 河北省自然科學(xué)基金(H2013206292) 2014年國家級大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計劃項目(201410089015)~~
【分類號】：R114

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