齐墩果酸拮抗赭曲霉毒素A诱导的HEK293T细胞自噬性死亡

目的:探索齐墩果酸(oleanolic acid,OA)对赭曲霉毒素A(ochratoxin A,OTA)的肾细胞毒性的拮抗机制。方法:将实验分为6组(对照组、OTA组、OA组、OA预处理组、OA和OTA同时处理组和OA后处理组)处理人胚肾上皮细胞(HEK293T),通过测定细胞存活率确定OA的拮抗剂量为1 μmol/L,并进一步通过OA和OTA对活性氧簇(ROS)含量和自噬相关蛋白表达影响的研究,探明OA拮抗OTA诱导的HEK293T细胞毒性的机制。结果:低浓度的OA(1 μmol/L)能够显著提高细胞存活率(p<0.05)。虽然1 μmol/L OA不会明显诱导ROS产生和激活自噬(p>0.05),但是能够通过调节p-mTOR、p-p70S6K、p-Beclin1和LC3的表达来不同程度缓解OTA诱导的HEK293T细胞的自噬性死亡,OA后处理方式效果最为明显(p<0.05)。结论:摄入含OA的食品能够对OTA诱导的肾细胞毒性有一定的拮抗作用。

Oleanolic Acid Antagonized Autophagic Death of HEK293T Cells Induced by Ochratoxin A

Objective:To explore the antagonism mechanism of oleanolic acid (OA) on the renal cytotoxicity of ochratoxin A (OTA). Methods:The experiment was divided into 6 groups (control group, OTA group, OA group, OA pretreatment group, OA and OTA simultaneous treatment group and OA post-treatment group) to treat human embryonic kidney epithelial cells (HEK293T). The amount of OA antagonist was determined to 1 μmol/L by measuring cell viability, and the effects of OA and OTA on the content of reactive oxygen species (ROS) and the expression of autophagy-related proteins were further investigated to elucidate the mechanism of OA antagonizing OTA-induced HEK293T cytotoxicity. Results:The low concentrations of OA (1 μmol/L) could significantly increase cell viability (p<0.05). Although 1 μmol/L OA did not significantly induce ROS production and activate autophagy (p>0.05), it could alleviate the autophagic death of OTA-induced HEK293T cells to different extents by regulating the expression of p-mTOR, p-p70S6K, p-Beclin1, and LC3.Post-processing of OA is the most effective method (p<0.05). Conclusion:To some extent, people can have some antagonistic effects on OTA-induced renal cytotoxicity by ingesting OA-containing foods.