Wang Xia, Song Xinhong, Si Youjiao, Xia Jikai, Wang Bin, Wang Peiyuan
Department of Pathology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China.
Exp Ther Med. 2018 Oct;16(4):3041-3049. doi: 10.3892/etm.2018.6564. Epub 2018 Aug 2.
Arecoline can be used to treat diseases including glaucoma and tapeworm infection, however, long-term administration can cause severe adverse effects, including oral submucosal fibrosis, oral cancer, hepatic injury and liver cancer. Autophagy serves a role in these injuries. The present study established a mouse model of arecoline-induced hepatic injury and investigated the role of autophagy-associated proteins in this injury. The results indicated that the expression levels of the autophagy marker protein microtubule associated protein 1 light chain 3 B (MAP1LC3B) and autophagy-promoting protein beclin 1 were elevated in the injured hepatic cells, while the expression levels of a well-known negative regulator of autophagy, mammalian target of rapamycin (mTOR), were reduced. Following treatment of the hepatic injury with glutathione, the liver function improved and liver damage was reduced effectively. Compared with the control group, the expression levels of both MAP1LC3B and beclin 1 were significantly upregulated in the glutathione-treated mice, but the expression of mTOR was significantly downregulated. It may be concluded that in the process of protecting against arecoline-induced hepatic injury, glutathione cooperates with mTOR and beclin 1 to accelerate autophagy, maintaining stable cell morphology and cellular functions.
槟榔碱可用于治疗包括青光眼和绦虫感染在内的疾病，然而，长期给药可导致严重的不良反应，包括口腔黏膜下纤维化、口腔癌、肝损伤和肝癌。自噬在这些损伤中起作用。本研究建立了槟榔碱诱导的肝损伤小鼠模型，并研究了自噬相关蛋白在该损伤中的作用。结果表明，自噬标记蛋白微管相关蛋白1轻链3B（MAP1LC3B）和自噬促进蛋白贝克林1在受损肝细胞中的表达水平升高，而自噬的著名负调控因子哺乳动物雷帕霉素靶蛋白（mTOR）的表达水平降低。用谷胱甘肽治疗肝损伤后，肝功能改善，肝损伤有效减轻。与对照组相比，谷胱甘肽治疗的小鼠中MAP1LC3B和贝克林1的表达水平均显著上调，但mTOR的表达显著下调。可以得出结论，在预防槟榔碱诱导的肝损伤过程中，谷胱甘肽与mTOR和贝克林1协同作用以加速自噬，维持细胞形态和细胞功能的稳定。
