细胞自噬在砷暴露所致肺损伤中的作用

苏鑫; 王春虾; 王素华; 郑姗姗; 刘建国; 余艳琴

doi:10.13421/j.cnki.hjwsxzz.2015.04.007

细胞自噬在砷暴露所致肺损伤中的作用

Role of Autophagy in Rats Lung Injury Induced by Arsenic Exposure

摘要

摘要:
目的探讨细胞自噬在砷暴露所致大鼠肺损伤中的作用。
方法 24只无特定病原体(SPF)级健康雄性SD大鼠随机分为4组, 即对照组, 砷暴露低(10 μg/L)、中(100 μg/L)、高(1000 μg/L)剂量组, 砷暴露组通过自由饮用含NaAsO₂的水进行染毒, 对照组自由饮用不含NaAsO₂的水, 染毒28 d后统一处死。ELISA法测定支气管肺泡灌洗液(BALF)中TNF-ɑ、IL-6、IL-8、IL-10的含量。Western blot法检测肺组织中自噬相关蛋白NBR1、p62、LC3Ⅱ表达量。
结果砷暴露组大鼠BALF中促炎因子TNF-a、IL6、IL8表达量显著高于对照组(P < 0.05), 且100 μg/L组的IL-6最高; 砷暴露1000 μg/L组的抑炎因子IL-10含量显著低于对照组(P < 0.05);与对照组相比砷暴露组大鼠肺组织中p62、NBR1的表达量增加(P < 0.05), 且存在剂量-反应关系; 与对照组相比砷暴露组大鼠肺组织中LC3Ⅱ蛋白表达量显著下降(P < 0.05), 且存在剂量-反应关系。
结论砷暴露所致大鼠肺损伤中, 细胞自噬被抑制时会加重大鼠肺部的炎症损伤, 当NaAsO₂暴露浓度达到100 μg/L时, 会对大鼠肺组织造成明显的损伤。

Abstract:
Objectives To study the role of autophagy in the lung injury of rats induced by arsenic exposure.
Methods Twenty four specific pathogen free (SPF) healthy male SD rats were randomly divided into four groups, namely the control group, the low (10 μg/L), medium (100 μg/L) and high (1000 μg/L) arsenic exposure groups. Arsenic exposure groups were intoxicated by sodium arsenite (NaAsO₂) in drinking water for 28 days. The level of TNF-α, IL-6, IL-8 and IL-10 in bronchoalveolar lavage fluid (BALF) were determined by ELISA and the expression of NBR1, p62 and LC3Ⅱrelated to the autophagy in lung tissue were determined by Western Blot.
Results The expression of proinflammatory cytokines TNF-a, IL6 and IL8 in arsenic exposure groups were significantly higher than that in the control group (P < 0.05). The level of IL6 in the medium arsenic exposure group (100 μg/L) was the highest and the level of IL-10 in the high arsenic exposure group (1000 μg/L) was significantly lower than the control group (P < 0.05). Compared with the control group, the expression of p62 and NBR1 in the lung tissue of arsenic exposure groups was higher (P < 0.05), and there was a dose-response relationship. In contrast, compared with the control group, the expression of LC3Ⅱ in the lung tissue of arsenic exposure groups were lower (P < 0.05), and there was a dose-response relationship too.
Conclusions The exposure of rats to arsenic would increase the inflammation of lung tissue when the autophagy was inhibited. In particular, when the concentration of NaAsO₂reaching to 100 μg/L, the damage of lung tissue in rats was more severe.

HTML全文

参考文献(19)

施引文献

资源附件(0)