摘要
目的探讨大鼠吸入染毒1-溴丙烷（1-BP）对肝脏和血液系统的毒性效应特点。方法无特定病原体级雄性Wistar大鼠48只随机分为对照组和低、中、高剂量组。4组分别给予质量浓度为0、1 250、2 500、5 000 mg/m3的1-BP连续动式吸入染毒,每天染毒8 h,每周5 d,共4周。染毒期间称取大鼠体质量,染毒结束后腹主动脉采血处死大鼠,每组随机取9只大鼠分离脏器检测脏器系数,检测血清生化和血常规;每组另3只大鼠进行脏器和骨髓病理组织学检查,并采用Tunel法进行肝细胞凋亡检测。结果染毒处理和染毒时间的交互效应有统计学意义（P〈0.01）;中剂量组大鼠第1、3、4周体质量均低于对照组（P〈0.05）,第4周体质量低于低剂量组（P〈0.05）;高剂量组第1周体质量分别低于对照组和低剂量组（P〈0.01）,第2~4周体质量均低于其余3组（P〈0.01）,染毒期间该组大鼠体质量无增加。对照组和低、中和高剂量组4组大鼠肝脏器系数分别为（3.015±0.160）%、（3.396±0.395）%、（3.860±0.663）%和（4.360±0.174）%;肝脏器系数和染毒剂量呈剂量-效应关系（P〈0.05）。4组大鼠血清丙氨酸氨基转移酶（ALT）活力分别为（41.73±2.83）、（49.09±2.51）、（58.71±2.21）和（72.45±9.28）U/L,天冬氨酸氨基转移酶（AST）活力分别为（166.64±9.94）、（193.55±9.51）、（219.70±4.01）和（259.27±18.49）U/L;ALT和AST活力均和染毒剂量呈剂量-效应关系（P〈0.05）。4组大鼠红细胞（RBC）计数分别为（7.18±0.82）×10^12/L、（7.25±0.17）×10^12/L、（7.19±0.18）×10^12/L和（6.63±0.36）×10^12/L,血红蛋白（Hb）分别为（139.67±3.00）、（137.44±3.75）、（137.89±3.59）和（126.78±6.14）g/L;高剂量组RBC计数和Hb均低于其余3组（P〈0.05）。病理组织学检查显示：3个剂量组大鼠均可见不同程度的肝细胞水肿,以高剂量组的细胞水肿程度最严重,同时,高剂量组大鼠脾脏的髓质吞噬细胞内可见较多含铁血黄素颗粒。肝细胞凋亡检测结果显示,高剂量组的肝组织表层可见较多Tunel阳性的凋亡细胞,其余3组大鼠肝组织均可见较多Tunel阴性的非凋亡细胞。结论吸入染毒1-BP对大鼠具有肝和血液毒性。肝脏是1-BP重要的毒效应靶器官,1-BP对肝脏的毒性作用存在剂量-效应关系。
Objective To explore the toxic characteristics of hepatotoxicity and hematological toxicity induced by 1-bromopropane（1-BP） inhalation exposure in rats. Methods Forty-eight specific pathogen free Wistar male rats were randomly divided into control group and low-,medium- and high- dose groups,and then respectively exposed to 1-BP vapor for 4 weeks（8 h /day,5 days /week） at the concentrations of 0,1 250,2 500 and 5 000 mg /m3 in a dynamic inhalation chamber system. Rats were sacrificed at the end of exposure,organ weights /coefficients,blood biochemical indexes and blood routine were examined in 9 rats per group,while pathological changes were observed and hepatocellular apoptosis was determined with Tunel method in 3 rats per group. Results The interaction of exposure groups and time was statistically significant（P〈0. 01）. The body weights of medium-dose groups were lower than those of the control group in the 1st,3rd,4th weeks（P〈0. 05）,and lower than those of the low-dose group in the 4th week（P〈0.05）. The body weights of high-dose group were lower than those of the control and low-dose groups in the 1st week respectively（ P〈0.01）,and lower than the other groups from the 2nd to the 4th weeks（P〈0.01）. The body weight of high-dose group did not increase during the exposure. The coefficient of live of the control,low-dose,medium-dose and high-dose groups were（3. 015 ±0. 160） %,（3. 396 ± 0. 395） %,（3. 860 ± 0. 663） % and（4. 360 ± 0. 174） % respectively. Coefficient of liver and exposure dose showed a dose-effect relationship（ P 0. 05）. The levels of alanine aminotransferase（ ALT） of 4 groups were（41. 73 ± 2. 83）,（49. 09 ± 2. 51）,（58. 71 ± 2. 21） and（72. 45 ± 9. 28） U /L while aspartic transaminase（ AST）were（166. 64 ± 9. 94）,（193. 55 ± 9. 51）,（219. 70 ± 4. 01） and（259. 27 ± 18. 49） U /L. Both of the levels of ALT,AST and exposure dose demonstrated dose-effect relationships respectively（P 0. 05）. Red blood cell counts of 4 groups were（7. 18 ± 0. 82） × 10^12/L,（7. 25 ± 0. 17） × 10^12/L,（7. 19 ± 0. 18） × 10^12/L and（6. 63 ± 0. 36） × 10^12/L while the hemoglobin levels were（139. 67 ± 3. 00）,（137. 44 ± 3. 75）,（137. 89 ± 3. 59） and（126. 78 ± 6. 14） g /L. Both of the red blood cell counts and hemoglobin level in the high-dose group were significantly decreased compared with those of the other groups respectively（P 0. 05）. Pathology examination results showed that there was different dropsy in liver cells in the 3 dose groups,especially much severe in high-dose group,where medulla with hemosiderin particles in phagocytes could be seen in spleen. Tunel assay showed more apparent positive apoptotic cells in the high-dose group while there were more negative non-apoptosis cells found in other groups. Conclusion 1-BP might induce hepatotoxicity and hematological toxicity by inhalation exposure in rats. Liver is an important target organ of 1-BP toxic effect. The toxic effect induced by1-BP on the liver shows a dose-effect relationship.
出处
《中国职业医学》
CAS
北大核心
2014年第4期367-373,共7页
China Occupational Medicine
基金
国家自然科学基金(81202246
30972459)
广东省职业病防治重点实验室(2012A061400007)
广东省自然科学基金项目(8151030005000004)
广东省医学科学技术研究基金(B2011023)
广东省职业病防治院科研项目(Z200908)
关键词
1-溴丙烷
肝毒性
血液毒性
细胞水肿
凋亡
剂量-效应关系
1-Bromopropane
Hepatotoxicity
Hematological toxicity
Cellular edema
Apoptosis
Dose-effect relationship
