摘要
目的:探讨水砷暴露与大鼠肝脏损伤的关系,了解激活素A(ACTA),转化生长因子-β1(TGF-β1)在肝脏损伤中的作用.方法:大鼠110只随机分成对照组、模型组(浓度100mg/L的亚砷酸钠溶液)、自然恢复组.对照组和模型组分别予第1、2、3、4月末各处死10只,自然恢复组第1月给予砷溶液,月末随机取出10只改为自来水,其余仍给予砷溶液.第2月末处死上月分出的10只,并在此取出10只改为自来水,1mo后处死,依次类推,第4月末将最后10只停用砷溶液的大鼠处死.股动脉取血进行血清肝功能和肝组织病理学检查以观察其肝脏损伤的动态变化,取大鼠肝组织采用实时荧光定量PCR法检测ACTA、TGF-β1的基因表达水平.结果:砷暴露1mo后脱离自然恢复1mo可见炎细胞浸润明显减轻.ALT、AST模型组中增高,第3、4月造模,ALT升高差异有统计学意义(P<0.05);造模1、2、3mo后分别自然恢复1mo,ALT降低有统计学意义(49.33±13.51U/Lvs62.68±23.57U/L,62.75±14.40U/Lvs64.36±18.24U/L,65.74±11.85U/Lvs69.36±15.7U/L,均P<0.05).ACTAmRNA第3、4月造模与对照组比较有统计学意义(64.83±28.29vs28.33±18.70,98.67±26.80vs28.33±18.70,均P<0.05),TGF-β1mRNA1、2、3、4mo造模与对照组比较均有统计学意义(46.27±18.39vs33.64±20.17,67.06±20.79vs33.64±20.17,88.33±23.42vs33.64±20.17,110.57±24.23vs33.64±20.17,均P<0.05);造模1、2、3mo后分别自然恢复1mo,TGF-β1mRNA降低有统计学意义(35.36±16.48vs46.27±18.39,52.04±21.37vs67.06±20.79,70.69±35.27vs88.33±23.42,均P<0.05).结论:砷暴露所引起的肝脏损伤随暴露时间的延长而加重,越早脱离暴露其损伤的肝细胞修复越快;促炎症因子ACTA、TGF-β1与砷暴露肝损伤的发生相关.
AIM： To investigate the relationship of arsenic- exposure to liver injury in rats, and to understand the effects of activin A （ACTA） and transforming growth factor-β1 （TGF-β1） on liver injury. METHODS： One hundred and ten rats were randomly divided into control group, model group （NaASO2 100 mg/L ） and spontaneous recovery group. Ten rats in control group and model group were sacrificed at the end of 1^st, 2^ed, 3^rd and 4^th months. Spontaneous recovery group was given sodium arsenite solution for the first month. Ten rats in spontaneous recovery group were randomly chosen and given tap water, then were sacrificed one month later and the rest were still given sodium arsenite solution after the first month. Then, another 10 rats of the rest were given tap water and then sacrificed one month later. The last 10 rats were sacrificed at the end of the fourth month. The rats were sacrificed for the liver function and pathologic examination of hepatic tissue. Real-time RT-PCR was used to examine the expression of ACTA and TGF-β1mRNA in hepatic tissue of rats. RESULTS： Liver injury in this spontaneous recovery at the end of the one-month arsenic- exposure was significantly relieved. Serum ALT and AST were significantly higher in model group than in control group （P 〈 0.05）. Serum ALT in spontaneous recovery one month at the end of the one, two, three-month arsenic- exposed group was lower than that of the one, two, three-month arsenic-exposed group （49.33 ±13.51 U/L vs 62.68 ± 23.57 U/L, 62.75 ± 14.40 U/L vs 64.36 ± 18.24 U/L, 65.74 ±11.85 U/L vs 69.36 ± 15.7 U/L, all P 〈 0.05）. ACTA mRNA ex- pression was significantly higher in 3, 4-model groups than those of control group （64.83 ± 28.29 vs 28.33 ± 18.70, 98.67 ± 26.80 vs 28.33 ± 18.70, both P 〈 0.05）. Compared with model group, TGF-β expressions in one, two, three-month ar- senic-exposed groups had statistically significant difference. （46.27 ± 18.39 vs 33.64 ± 20.17, 67.06 ± 20.79 vs 33.64 ± 20.17, 88.33 ± 23.42 vs 33.64 ± 20.17, 110.57 ± 24.23 vs 33.64 ± 20.17, all P 〈 0.05）. The expression of TGF-β1 mRNA was lower in this spontaneous recovery one month at the end of the one, two, three-arsenic-exposed groups compared with those in the the, two, three- arsenic-exposed groups （35.36 ± 16.48 vs 46.27 ± 18.39, 52.04 ± 21.37 vs 67.06 ± 20.79, 70.69 ± 35.27 vs 88.33 ± 23.42, all P 〈 0.05）. CONCLUSION： Liver tissue injury is aggravated greatly with the extension of arsenic-exposed by this experiment in a time-dependent man-ner. ACTA and TGF-β1 are correlated to arsenic-exposed hepatic injury.
出处
《世界华人消化杂志》
CAS
北大核心
2009年第8期747-752,共6页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.30471592
中国肝炎防治基金会"王宝恩肝纤维化研究基金"资助项目
No.20070013~~
关键词
砷
肝脏
激活素A
转化生长因子-Β1
Key Words： Arsenic
Liver
Activin A
Transforminggrowth factor-β1
