氟氯氰菊酯通过cGAS-STING信号通路诱导肺损伤  

Cyfluthrin Induces Lung Injury through cGAS-STING Signaling Pathway

作　　者：宋亚男 倪文思 朱玲勤[1,2] 王瑞 孙祎平[1,2] 杨惠芳 SONG Ya’nan;NI Wensi;ZHU Lingqin;WANG Rui;SUN Yiping;YANG Huifang(Department of Occupational and Environmental Health,School of Public Healthy and Management,Ningxia Medical University,Yinchuan 750004,China;Key Laboratory of Environmental Factors and Chronic Disease Control,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学公共卫生与管理学院,银川750004 [2]宁夏医科大学环境因素与慢性病控制重点实验室,银川750004

出　　处：《宁夏医科大学学报》2023年第3期268-274,共7页Journal of Ningxia Medical University

基　　金：国家自然科学基金项目(81960584)。

摘　　要：目的 探讨氟氯氰菊酯诱导肺损伤及其相关机制。方法 40只SPF级SD大鼠,随机分为4组,即对照组、氟氯氰菊酯低剂量染毒组、中剂量染毒组、高剂量染毒组,雌雄各半。染毒4周后,HE染色观察大鼠的肺组织形态变化;透射电镜观察肺组织超微结构变化;通过称重观察大鼠体质量变化趋势和肺脏器系数;检测肺组织匀浆中丙二醛(MDA)和超氧化物歧化酶(SOD)含量的变化;采用Western blot、qPCR检测乙醛脱氢酶2(ALDH2)、环状GMP-AMP合成酶(cGAS)、干扰素刺激基因(STING)、核因子κB(NFκB)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的蛋白及mRNA表达水平变化。结果 氟氯氰菊酯暴露高剂量组体质量减轻,中剂量组和高剂量组肺脏系数增加(P均<0.05)。HE染色结果显示氟氯氰菊酯暴露组肺组织和细胞结构受损。与对照组比较,暴露组MDA表达量升高,SOD、ALDH2表达量降低(P均<0.05)。与对照组相比,暴露组肺组织中cGAS、STING、NFκB、TNF-α、IL-6 mRNA和蛋白表达水平均升高(P均<0.05)。结论 氟氯氰菊酯可引起肺组织损伤,与cGAS-STING通路激活有关。Objective To explore the mechanism of cyfluthrin induced lung injury.Methods Forty SPF SD rats were randomly divided into 4 groups,including control group,cyfluthrin low-dose group,medium-dose group and high-dose group(half male and half female).After 4 weeks of exposure,HE staining was performed to observe the morphological changes of lung tissue.Ultrastructural changes of lung tissue cells were checked under transmission electron microscope.The change trend of body weight and lung coefficient of rats were observed by weighing.The content changes of malondialdehyde(MDA)and superoxide dismutase(SOD)in lung homogenate were determined by kits.Western blot and qPCR were used to detect acetaldehyde dehydrogenase 2(ALDH2),cyclic GMP-AMP synthetase(cGAS),interferon stimulating gene(STING),nuclear factorκB(NFκB),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)protein and mRNA expression levels.Results Body weight was decreased in the high-dose group and lung coefficients were increased in the medium-dose and high-dose groups(P all<0.05).Pathological examination showed that lung tissue and cell structure were impaired in the cyfluthrin exposed group.Compared with the control group,MDA expression was increased in exposed group,while SOD and ALDH2 expression was decreased,and the difference was statistically significant(P all<0.05).Compared with the control group,mRNA levels of cGAS,STING,NFκB,TNF-αand IL-6 and protein expression levels of cGAS,STING,NFκB,TNF-αand IL-6 in lung tissues of exposed group were increased,and the differences were statistically significant(P all<0.05).Conclusion The mechanism that cyfluthrin can cause lung injury may lie in its activation of cGAS-STING pathway to cause inflammation.

关 键 词：氟氯氰菊酯 肺损伤 氧化应激 炎症 cGAS-STING信号通路 

分 类 号：R114[医药卫生—卫生毒理学]