p53介导的线粒体凋亡通路在燃煤型砷中毒大鼠肝损伤中的作用  

Role of p53-mediated mitochondrial apoptotic pathway in arsenic liver injury caused by coal-burning

作　　者：谢婷婷[1] 张爱华[1] 

机构地区：[1]贵阳医学院公共卫生学院毒理学教研室,贵州贵阳550004

出　　处：《中国药理学与毒理学杂志》2014年第2期210-215,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81172603);贵州省基金(黔科合人才团队20124003);贵州省基金(黔教科2008020);教育厅研究生教育创新基金(0215016)~~

摘　　要：目的了解燃煤型砷中毒大鼠肝细胞凋亡情况及p53介导的线粒体凋亡通路在砷致肝损伤中的作用。方法 Wistar大鼠喂饲含砷量分别为0,25,50和100 mg·kg-1的饲料,连续90 d。采用氢化物发生-电感耦合等离子发射光谱法检测尿砷、毛发砷含量;采用末端脱氧核糖核苷酸转移酶介导的缺口末端标记法检测肝细胞凋亡情况;采用实时荧光定量PCR检测外周血和肝组织p53,Bax,Bcl2 mRNA表达水平;采用Western blot检测肝组织p53,Bax,Bcl2蛋白水平。结果随染砷剂量增加,大鼠尿砷、毛发砷含量逐渐增高,与正常对照组比较,差异有统计学意义。砷50,100 mg·kg-1组肝细胞凋亡率(分别为16.49±2.06,15.83±1.28)高于砷0,25 mg·kg-1组(分别为9.00±0.59,9.27±0.36),差异有统计学意义(P<0.05)。砷100 mg·kg-1组外周血p53 mRNA相对表达量(2.69±1.84)和砷25,50,100 mg·kg-1组肝组织p53 mRNA相对表达量(分别为1.63±0.28,1.91±0.38,1.71±0.18)均高于正常对照组(分别为0.86±0.15,1.22±0.12);砷50,100 mg·kg-1组外周血Bax mRNA相对表达量(分别为1.36±0.30,1.94±0.65)和砷100 mg·kg-1组肝组织Bax mRNA相对表达量(1.34±0.23)均高于正常对照组(分别为0.77±0.15,0.84±0.34);砷100 mg·kg-1组肝组织Bcl2 mRNA相对表达量(0.98±0.50)低于正常对照组(2.14±1.15),差异有统计学意义(P<0.05)。砷25,50和100 mg·kg-1组肝组织p53蛋白相对表达量(分别为1.06±0.56,1.15±0.77和0.74±0.27),砷50和100 mg·kg-1组肝组织Bax蛋白相对表达量(分别为0.74±0.43和0.69±0.37),均高于正常对照组(分别为0.36±0.19和0.25±0.09),差异均有统计学意义(P<0.05)。结论燃煤砷暴露所致肝损伤可能与砷通过p53调控Bax和Bcl2的表达水平诱导肝细胞凋亡机制有关。OBJECTIVE To investigate the apoptosis of hepatocytes in arsenic poisoning rats caused by coal-burning and explore the effects of p53-induced mitochondrial apoptotic pathway on arsenic liver injury.METHODS Wistar rats were fed with 164.74 pp m arsenic conta minated grain at the levels of 15%,30% and 60% （arsenic contents were 25,50 and 100 mg·kg -1 ,respectively）for 90 d. The arsenic contents of urine and hair,apoptosis of hepatocytes and mRNA expression of p53,Bax and Bcl2 in peripheral blood and hepatocytes were evaluated.At the sa me ti me,protein expression of p53, Bax and Bcl2 in hepatocytes were analyzed.RESULTS The arsenic contents of urine and hair increased with the elevation of arsenic dose.The apoptotic rate of hepatocytes in arsenic 50 and 100 mg·kg -1 group were 16.49 ±2.06 and 15.83 ±1 .28,respectively which were significantly higher than the control group and arsenic 25 mg·kg -1 group （9.00 ±0.59 and 9.27 ±0.36,respectively,P ＆lt;0.05）.p53 mRNA expression of peripheral blood in arsenic 100 mg·kg -1 group was 2.69 ±1 .84 while p53 mRNA expression of hepatocytes in arsenic 25,50 and 100 mg·kg -1 group were 1 .63 ±0.28, 1 .91 ±0.38 and 1 .71 ±0.18,respectively which were significantly higher than the control group （0.86 ± 0.15 and 1 .22 ±0.12,respectively,〈0.05）.Bax mRNA expression of peripheral blood in arsenic 50 and 100 mg·kg -1 group were 1 .36 ±0.30 and 1 .94 ±0.65 while Bax mRNA expression of hepatocytes in arsenic 100 mg·kg -1 group was 1 .34 ±0.23 which were significantly higher than the control group （0.77 ±0.15 and 0.84 ±0.34,respectively,〈0.05）.Bcl2 mRNA expression of hepatocytes in arse-nic 100 mg·kg -1 group was 0.98 ±0.50 which was significantly lower than the control group （2.14 ± 1 .15,〈0.05）.p53 protein expression of hepatocytes in arsenic 25,50 and 100 mg·kg -1 group were 1 .06 ±0.56,1 .15 ±0.77 and 0.74 ±0.27,respectively while Bax protein expression of hepatocytes in arsenic 50 and 100 mg·kg -1 group were 0.74 ±0.43 and 0.6

关 键 词：砷中毒 煤 基因 p53 细胞凋亡 肝损伤 

分 类 号：R599[医药卫生—内科学]