目的 探讨槲皮素通过调节Drp1的表达改善线粒体自噬对苯并芘(BaP)损伤人肺腺癌细胞(A549)的保护作用。方法 取A549细胞随机分为Control组(常规培养)、BaP组(BaP处理)、BaP+Quercetin组(槲皮素干预+BaP处理)、BaP+Mdivi-1组(Drp1抑制剂Mdivi-1+BaP处理)。CCK8法测定细胞活力、TUNEL染色观察细胞凋亡情况、鬼笔环肽染色观察细胞体积、透射电镜观察细胞器的变化、Western印迹法观察自噬相关蛋白(Drp1、PINK1、Parkin)的表达。结果 与Control组相比,BaP组细胞活力降低(P＜0.05),细胞凋亡率、自噬相关蛋白(Drp1、PINK1、Parkin)表达量均升高(P＜0.05);与BaP组相比,BaP+Quercetin组、BaP+Mdivi-1组细胞活力升高(P＜0.05),细胞凋亡率、自噬相关蛋白(Drp1、PINK1、Parkin)表达量均降低(P＜0.05)。结论 槲皮素能通过调节Drp1的表达,改善线粒体自噬异常,实现对BaP诱导的A549细胞损伤的保护作用。
Abstract
Objective To investigate the protective effect of quercetin against benzo(a)pyrene (BaP)-induced damage in human lung adenocarcinoma A549 cells by regulating Drp1 expression to improve mitophagy. Methods The A549 cells were randomly divided into 4 groups: a control group (normal culture), a BaP group (treated with BaP), a BaP+Quercetin group (quercetin intervention + BaP treatment), and a BaP+Mdivi-1 group (Drp1 inhibitor Mdivi-1 + BaP treatment). Cell viability was measured by CCK8 assay, apoptosis was observed by TUNEL staining, cell volume was observed by phalloidin staining, changes in organelles were examined by transmission electron microscopy, and the expression levels of autophagy-related proteins (Drp1, PINK1, Parkin) was analyzed by Western blotting. Results Compared with the Control group, the BaP group showed reduced cell viability (P<0.05), increased apoptosis rate and elevated expression of autophagy-related proteins (Drp1, PINK1, Parkin) increased (P<0.05). Compared with the BaP group, the cell viability in the BaP + Quercetin group and the BaP + Mdivi-1 group increased (P<0.05), and the apoptosis rate and the expression of autophagy-related proteins (Drp1, PINK1, Parkin) decreased (P<0.05). Conclusions Quercetin can regulate the expression of Drp1 to improve abnormal mitophagy and achieve the protective effect on A549 cells damage induced by BaP.
关键词
Drp1 /
线粒体自噬 /
槲皮素 /
苯并芘 /
肺腺癌
Key words
Drp1 /
mitophagy /
quercetin /
benzo(a)pyrene /
lung adenocarcinoma
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基金
天津市医学重点学科建设资助(TJYXZDXK-3-001D)
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