siRNA干扰β-catenin对亚砷酸钠致大鼠肺组织病变的影响

Effects of siRNA-interfered β-catenin on lesions induced by sodium arsenite in lung tissue of rats

目的探讨通过si RNA干扰β-catenin对亚砷酸钠致大鼠体内砷水平和肺组织病变的影响。方法将32只健康成年SPF级SD大鼠按体重随机分为对照(超纯水)组、染砷空白对照组、染砷+β-catenin干扰组和染砷+阴性转染对照组,每组8只,雌雄各半。采用自由饮水方式染毒亚砷酸钠溶液(11.25 mg/kg),连续染毒16周;在最后1周,腹腔注射β-catenin si RNA转染试剂和阴性对照转染试剂(0.49μg/g),连续1周。观察大鼠肺组织病理学改变,检测大鼠血砷、尿砷和肺组织砷水平。结果染砷第16周,染砷空白对照组、染砷+β-catenin干扰组和染砷+阴性转染对照组大鼠体重较对照组减轻(P<0.05)。染砷+β-catenin干扰组大鼠肺组织病理损伤较染砷空白对照组和染砷+阴性转染对照组严重,出现大部分纤维化,肺泡结构几乎消失。染砷空白对照组、染砷+β-catenin干扰组和染砷+阴性转染对照组大鼠血砷、尿砷和肺组织砷水平较对照组增加(P<0.05)。染砷+β-catenin干扰组大鼠血砷、尿砷和肺组织砷水平较染砷+阴性转染对照组增加(P<0.05);其中雄性大鼠肺组织砷含量较染砷空白对照组增加(P<0.05)。结论长期砷暴露致大鼠肺组织病变;而干扰β-catenin基因后可能增加砷的蓄积,加重大鼠肺组织病变。

Objective To investigate the effects ofβ-catenin treated with si RNA interference on arsenic levels and lung pathological changes in rats induced by sodium arsenite.Methods Thirty-two healthy adult SPF(specefic pathogen free)grade SD rats were randomly divided into control group(ultrapure water),arsenic-exposed blank control group,arsenic-exposedβ-catenin interference group and arsenic-exposed negative transfection control group according to body weight,eight in each,half male and female.Sodium arsenite(11.25 mg/kg)was given to the rats through drinking water for 16 consecutive weeks.At the last week of treatment,β-catenin si RNA transfection reagent and negative control transfection reagent(0.49μg/g)were injected intraperitoneally continuously.The pathological changes of lung tissue in rats was examined,and the arsenic level in blood,urine and lung tissue of rats was determined.Results At the 16 th week of arsenic exposure,the body weight of rats in arsenic-exposed blank control group,arsenic-exposedβ-catenin interference group and arsenic-exposed negative transfection control group were lower than the control group(P<0.05).Arsenic-exposedβ-catenin interference group showed more severe pathological changes in lung tissue compared with arsenic-exposed blank control group and arsenic-exposed negative transfectin control group,most of the lung tissue showed fibrotic chages and the alveolar structure almost disappeared.The level of arsenic in blood,urine and lung tissue in arsenic-exposed blank control group,arsenic-exposedβ-catenin interference group and arsenic-exposed negative control transfection group were significantly higher than those of control group(P<0.05).The arsenic level in blood urine and lung tissue in arsenic-exposedβ-catenin interference group was higher than that of arsenicexposed negative transfectin control group(P<0.05),and the arsenic content in lung tissue of male rats was higher than that of arsenic-exposed blank control group(P<0.05).Conclusion Long-term arsenic exposure may induce lung tissue lesions in rats,while interference forβ-catenin gene may increase arsenic accumulation and aggravate lung tissue lesions in rats.