饮水砷暴露大鼠血清炎症因子及肺泡灌洗液中自噬相关蛋白NBR1与P62的表达

Expression of inflammatory factors in serum and autophagy-related protein NBR1 and P62 in alveolar lavage fluid of rats exposed to arsenic through drinking water

目的观察亚砷酸钠对大鼠血清炎症因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子(TNF-α)和肺泡灌洗液中自噬相关蛋白NBR1、P62的影响。方法将32只健康SPF级雄性SD大鼠按体重随机分为4组,分别为对照(超纯水)组和10、100、1 000μg/L亚砷酸钠染毒组,每组8只。采用自由饮用方式染毒,连续染毒28 d。测定大鼠血清中IL-6、IL-8、IL-1β、TNF-α的浓度和肺泡灌洗液中NBR1和P62的水平。结果与对照组比较,各浓度亚砷酸钠染毒组大鼠血清中IL-1β、IL-6的水平和10、100μg/L亚砷酸钠染毒组大鼠血清中IL-8水平及10μg/L亚砷酸钠染毒组大鼠血清中TNF-α水平较高,差异均有统计学意义(P<0.05);且随着亚砷酸钠染毒浓度的升高,大鼠血清中IL-6、IL-8和TNF-α的浓度均呈先升高后下降趋势。与对照组比较,100、1 000μg/L亚砷酸钠染毒组大鼠肺泡灌洗液中NBR1的水平和10、100μg/L亚砷酸钠染毒组大鼠肺泡灌洗液中P62的水平较高,差异均有统计学意义(P<0.05);且随着亚砷酸钠染毒浓度的升高,大鼠肺泡灌洗液中NBR1、P62的浓度均呈先升高后下降趋势。亚砷酸钠染毒大鼠血清IL-6与肺泡灌洗液中P62呈正相关(r=0.399,P<0.05),血清TNF-α与肺泡灌洗液中NBR1呈正相关(r=0.452,P<0.05)。结论炎症因子和细胞自噬参与亚砷酸钠致大鼠肺损伤,大鼠肺部损伤可能与细胞自噬受到抑制和炎症因子增多有关。

Objective To observe the effects of sodium arsenite on interleukin-1 β (IL-1β),interleukin-6(IL-6),interleukin-8(IL-8) tumor necrosis factor(TNF-α) in serum and the autophagy-associated protein(NBR1,P62) in alveolar lavage fluid(ALF) of rats. Methods A total of 32 SPF-grade healthy male SD rats were randomly divided into four groups,control group(ultrapure water),10,100,and 1 000 μg/L NaAsO2 groups,eight in each group,free drinking for 28 days.The concentrations of IL-6,IL-8,IL-1β,TNF-α in serum and the levels of NBR1 and P62 in alveolar lavage fluid were determined. Results Compared with the control group,the levels of IL-1β and IL-6 in the serum of exposure groups and the levels of IL-8 in serum of 10 and 100 μg/L NaAsO2 groups and the levels of TNF-α in serum of 10 μg/L NaAsO2 group were higher(P <0.05);With the increase of exposure doses,the levels of inflammatory factors in the serum of rats increased first and then decreased.Compared with the control group,the levels of NBR1 in ALF of rats in 100 and 1 000 μg/L NaAsO2 groups and the levels of P62 in ALF of rats in10 and 100 μg/L NaAsO2 groups were higher(P<0.05);With the increase of exposure doses,the levels of NBR1 and P62 in ALF of rats increased first and then decreased. Positive correlations were observed between serum IL-6 and P62 in ALF(r=0.399,P<0.05),serum TNF-α and NBR1 in ALF(r=0.452,P<0.05) among rats exposed to NaAsO2. Conclusion Inflammatory factors and autophagy are involved in lung injury induced by sodium arsenite in rats,which may be associated with inhibition of autophagy and increased inflammatory factors.