CAJ | 학술논문

目的运用一维磁共振氢谱(1H MR)结合模式识别的代谢组学技术探讨大鼠气管内注入纳米二氧化钛(nano-TiO2)的毒效应,并寻找毒效应的靶器官及生物标志物.方法将24只SD大鼠按数字表法随机分为4组,分别为高剂量组(40.0 mg/kg nano-TiO2)、中剂量组(4.0 mg/kg nano-riO2)、低剂量组(0.4 mg/kg nano-TiO2)和对照组(生理盐水),每组各6只大鼠.按0.1 ml/100 g采用非暴露式气管内注入方式,染毒1次.观察1周后,进行血浆1H MR检测,并对代谢图谱进行主成分分析(PCA).同时摘取心、肺、肝、肾等器官作组织病理学检查.结果血浆代谢组学分析表明:高剂量组乳酸相对含量[(37.86±2.58)×10-3]、柠檬酸相对含量[(2.21±0.45)×10-3]、胆碱相对含量[(7.74±0.76)×10-3]和肌酸相对含量[(4.17 d-1.15)×10-3]低于对照组[(52.07±5.12)×10-3、(3.01±0.21)×10-3、(9.28±0.78)×10-3、(8.59±2.64)×10-3](t值分别为-6.024、-3.177、-3.374、-4.215,P值均<0.05);而葡萄糖相对含量[(19.41±1.72)×10-3]高于对照组[(14.45±2.45)×10-3](t=2.802,P<0.05);中剂量组乳酸相对含量[(44.39±5.09)×10-3]和肌酸相对含量[(3.67±0.76)×10-3]低于对照组[(52.07±5.12)×10-3、(8.59±2.64)×10-3](t值分别为-3.254、-4.694,P值均<0.05);低剂量组丙酮酸相对含量[(3.84±0.70)×10-3]高于对照组[(3.13×±0.46)×10-3](t=2.787,P<0.05),胆碱相对含量[(8.10±0.72)×10-3]低于对照组[(9.28±0.78)×10-3](t=-2.602,P<0.05).各剂最组大鼠各个组织脏器均未见明显的病理变化.结论大鼠肺脏、肝脏、肾脏和心脏是nano-TiO2气管注入染毒的靶器官;乳酸、丙酮酸、匍萄糖、柠檬酸、胆碱和肌酸可作为寻找nano-TiO2致机体毒作用靶器官的参考生物标志物.
목적 운용일유자공진경보(1H MR)결합모식식별적대사조학기술탐토대서기관내주입납미이양화태(nano-TiO2)적독효응,병심조독효응적파기관급생물표지물.방법 장24지SD대서안수자표법수궤분위4조,분별위고제량조(40.0 mg/kg nano-TiO2)、중제량조(4.0 mg/kg nano-riO2)、저제량조(0.4 mg/kg nano-TiO2)화대조조(생리염수),매조각6지대서.안0.1 ml/100 g채용비폭로식기관내주입방식,염독1차.관찰1주후,진행혈장1H MR검측,병대대사도보진행주성분분석(PCA).동시적취심、폐、간、신등기관작조직병이학검사.결과 혈장대사조학분석표명:고제량조유산상대함량[(37.86±2.58)×10-3]、저몽산상대함량[(2.21±0.45)×10-3]、담감상대함량[(7.74±0.76)×10-3]화기산상대함량[(4.17 d-1.15)×10-3]저우대조조[(52.07±5.12)×10-3、(3.01±0.21)×10-3、(9.28±0.78)×10-3、(8.59±2.64)×10-3](t치분별위-6.024、-3.177、-3.374、-4.215,P치균<0.05);이포도당상대함량[(19.41±1.72)×10-3]고우대조조[(14.45±2.45)×10-3](t=2.802,P<0.05);중제량조유산상대함량[(44.39±5.09)×10-3]화기산상대함량[(3.67±0.76)×10-3]저우대조조[(52.07±5.12)×10-3、(8.59±2.64)×10-3](t치분별위-3.254、-4.694,P치균<0.05);저제량조병동산상대함량[(3.84±0.70)×10-3]고우대조조[(3.13×±0.46)×10-3](t=2.787,P<0.05),담감상대함량[(8.10±0.72)×10-3]저우대조조[(9.28±0.78)×10-3](t=-2.602,P<0.05).각제최조대서각개조직장기균미견명현적병리변화.결론 대서폐장、간장、신장화심장시nano-TiO2기관주입염독적파기관;유산、병동산、포도당、저몽산、담감화기산가작위심조nano-TiO2치궤체독작용파기관적삼고생물표지물.
Objective 1H magnetic resonance (1H MR) speetroseopic technique in combination with pattern recognition technique were applied to analyze toxic effects of rats which were intratracheally instilled with titanium dioxide nanoparticles (nano-TiO2) as well as to detect the target organs and biomarkers associated with the toxic effects. Methods Twenty-four SD male rats were divided into 4 groups randomly which were high dose group(40 mg/kg nano-TiO2), moderate dose group(4 mg/kg nano-TiO2), low dose group(0.4 mg/kg nano-TiO2) and control group (0.9% NaC1 solution) respectively,there were six rats per group. All rats were exposed to the object by single intratracheally instilling at a volume of 0.1 ml/ 100 g. After one week observation, 1H MR spectra of plasma were measured and analyzed by principal component analysis. Histopathologic examination for tissues such as heart, lung, liver, and kidney were performed simultaneously. Results The relative content of lactace [(37.86±2.58)×10-3], citrate [(2.21±0.45)×10-3],choline[(7.74±0.76)×10-3] and creatine[ (4.17±1.15)×10-3] in high dose group were significantly decreased as compared with those[(52.07±5.12)×10-3, (3.01±0.21)×10-3, (9.28±0.78)×10-3, (8.59±2.64)×10-3] in control group (t values were-6.024,-3.177, -3.374,-4.215 respectively, P<0.05), however the relative content of glucose [(19.41±1.72)×10-3] was significantly increased compared with that [(14.45±2.45)×10-3] in control group (t value was 2. 802,P<0.05). The relative content of lactace[(44.39±5.09)×10-3] land creatine [(3.67±0.76)×10-3] in moderate group was significantly decreased compared with those [(52.07±5.12)×10-3, (8.59±2.64)×10-3] in control group (t values were-3.254,-4.694 respectively, P<0.05). The relative content of pyruvate[(3.84±0.70)×10-3]was significantly increased in low dose group as compared with that [(3.13±0.46)×10-3] in control group (t value was 2.787, P<0.05), however the relative content of creatine [(8.10±0.72)×10-3] was significantly decreased compared with that [(9.28±0.78)×10-3] in control group (t value was -2.602, P<0.05). No significant difference was found between other experimental groups and control group. No visible damage was found in histopathologic examination. Conclusion Lung, liver, kidney and heart were the target organs of rats which were intratracheally instilling titanium dioxide nanoparticles. Lactate, pyruvate, glucose, citrate, choline and creatine can be presumed as the biomarkers when searching the target organs of the toxic effects.