摘要
目的探讨促炎症因子在慢性水砷暴露小鼠肝损伤中的作用。方法60只雄性小鼠按体质量随机分成对照组、亚砷酸钠组(iAs孙组,300mg/L)、砷酸钠组(iAs鼻组,300mg/L)。10个月后处死小鼠,肝功能检查血清丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、球蛋白(GLB);部分肝组织做HE染色;Trizol-酚-氯仿一步法提取肝组织总RNA,紫外分光光度法测定总RNA及纯度,实时荧光定量PCR法测定肝组织中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、环氧化酶2(COX-2)mRNA的表达,以18S基因作为质控。结果ALT、AST、GLB在对照组[(38.0±5.6)U/L、(118.3±9.1)U/L、(20.9±0.6)g/L]、iAs^3+组[(61.5±5.5)U/L、(530.9±39.0)U/L、(27.2±4.1)g/L]和iAs^5+组[(48.3±2.6)U/L、(243.9±13.6)U/L、(23.2±2.1)g/L]组间比较,差异均有统计学意义(F值分别为45.653、164.326、9.639,P〈0.05);ALT、AST组间两两比较差异均有统计学意义(P〈0.05),GLB仅在iAs如组与对照组比较差异有统计学意义(P〈0.05)。肝组织病理检查示有明显的炎症细胞浸润和肝细胞坏死.TNF-α、IL-6、COX-2mRNA的表达在对照组(11.84±3.21、41.08±22.98、26.60±5.84)、iAs^3+组(48.59±19.65、218.87±70.05、207.86±155.39)、iAs^5+组(35.56±10.84、84.15±28.38、18.88±6.34)组间比较,差异均有统计学意义(F值分别为24.317、49.611、8.499,P〈0.05)。结论长期砷暴露可导致肝脏的炎症反应、慢性肝损伤。TNF-α、IL-6、COX-2在iAs卦所导致的肝脏损伤中均起作用,其中TNF-α、IL-6炎症因子基因在iAs孙组肝组织的表达较iAss+组更明显。COX-2在iAs鼻组所导致的肝脏损伤中可能无明显作用。
Objective To investigate the effect of inflammatory mediator in mice chronically exposed to inorganic arsenate. Methods 60 mice were divided into control group, sodium arsenite group (iAs^3+ 300 mg/L) and sodium arsenite group(iAs^5+ 300 mg/L) at random, iAs^3+group and iAs^5+group were daily given sodium arsenite and sodium arsenate respectively. The mice were sacrificed after 10 monthes for liver function and pathologic examinations. Total RNA was extracted by the Trizol-Phenol-Chlorofor-method from liver tissue. The total RNA extracted from hepatic tissue was detected for its density and purity, as well as the expression of tumor necrosis factor-alpha (TNF-α) mRNA, Interleukin-6 (IL-6) mRNA, cyclooxygenase 2 ( COX-2 ) mRNA with real time fluorescence quantitative PCR. The results were controlled with 18S. Results Serum alanine aminitransperase (ALT), aspartate aminotransferase(AST), globulin(GLB) of arsenic exposed mice[iAs^3+group (61.5 ± 5.5)U/L, (530.9 ± 39.0)U/L, (27.2 ± 4.1)g/L, iAs^5+group (48.3 ± 2.6)U/L, (243.9 ± 13.6)U/L, (23.2 ± 2.1)g/L] were different from that of the normal mice [(38.0 ± 5.6)U/L, (118.3 ±9.1)U/L, (20.9 ± 0.6)g/L], the difference had statistical significances(F = 45.653,164.326,9.639, P〈 0.05). Serum ALT and serum AST had statistical significances among the three group(P 〈 0.05), serum GLB had statistical significance between iAs^3+group and the control group (P 〈 0.05). Pathologic examination identified notable inflammation and liver cell necrosis involved in arsenic groups. Compared with the control group (11.84 ± 3.21,41.08 ± 22.98,26.60 ± 5.84), the expression of TNF-α mRNA, IL-6 mRNA, COX-2 mRNA had statistical significance between iAs^3+group (48.59 ± 19.65,218.87 ± 70.05,207.86 ± 155.39) and iAs^5+group (35.56 ± 10.84,84.15 ± 28.38,18.88 ± 6.34), the difference had statistical significances(F= 24.317,49.611,8.499, P〈 0.05). Conclusions long-term exposure of mice to inorganic arsenate could result in inflammation and chronic damage of liver. The inflammation induced by iAs^3+is more severe than that by iAs^5+
出处
《中国地方病学杂志》
CAS
CSCD
北大核心
2008年第1期15-18,共4页
Chinese Jouranl of Endemiology
基金
国家自然科学基金(30471592)
科技部国际科技合作与交流专项经费项目(2005DFA30640,A类)
关键词
砷中毒
饮水
肿瘤坏死因子Α
白细胞介素6
环氧化酶2
肝损伤
Arsenic poisoning
Drinking
Tumor necrosis factor-alpha
Interleukin-6
Cyclooxygenase 2
Liver injury