Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Guangdong Province Engineering Technology Research Institute of T.C.M., Guangzhou, 510095, China.
Phytother Res. 2018 Jul;32(7):1364-1372. doi: 10.1002/ptr.6070. Epub 2018 Mar 26.
This study was designed to investigate the precancerous lesions of gastric carcinoma (PLGC)-reversing mechanisms of astragaloside IV (ASIV) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced PLGC rats. All rats were sacrificed after 10-week treatment. Gastric tissue was analyzed by using histopathology and electron microscope. To be fully evidenced, LDHA, p53, TIGAR, MCT1, MCT4, HIF-1α, CD147, and miRNA-34a were detected by Western blotting and Real-time Quantitative polymerase chain reaction (RT-qPCR). As histopathology and electron microscope showed, it can be clearly observed that the area of dysplasia was reduced in ASIV groups, indicating that MNNG-induced PLGC was markedly reversed by ASIV. Moreover, compared with model group, a significant decrease in gene expressions of LDHA, MCT1, MCT4, HIF-1α, CD147, and TIGAR was observed whereas miRNA-34a level was increased in ASIV groups. A significant up-regulation induced by MNNG in protein levels of LDHA, MCT1, MCT4, HIF-1α, and CD147 was attenuated in rats treated with ASIV. In contrast, the decreased expression of TIGAR was restored by ASIV. Interestingly, up-regulation of p53 expression induced by MNNG was further increased in ASIV groups. In brief, these results implied that abnormal glycolysis was relieved by ASIV via regulation of the expressions of LDHA, p53, TIGAR, MCT1, MCT4, HIF-1α, CD147, and miRNA-34a.
本研究旨在探讨黄芪甲苷（ASIV）在 N-甲基-N'-硝基-N-亚硝基胍（MNNG）诱导的胃癌前病变（PLGC）大鼠中逆转的机制。所有大鼠在 10 周治疗后处死。通过组织病理学和电子显微镜分析胃组织。为了充分证明这一点，通过 Western blot 和实时定量聚合酶链反应（RT-qPCR）检测了 LDHA、p53、TIGAR、MCT1、MCT4、HIF-1α、CD147 和 miRNA-34a。组织病理学和电子显微镜显示，ASIV 组的异型增生面积减少，表明 ASIV 显著逆转了 MNNG 诱导的 PLGC。此外，与模型组相比，ASIV 组 LDHA、MCT1、MCT4、HIF-1α、CD147 和 TIGAR 的基因表达显著降低，而 miRNA-34a 水平升高。ASIV 减弱了 MNNG 诱导的 LDHA、MCT1、MCT4、HIF-1α 和 CD147 蛋白水平的显著上调。相反，ASIV 恢复了 TIGAR 的下调表达。有趣的是，MNNG 诱导的 p53 表达上调在 ASIV 组进一步增加。总之，这些结果表明，ASIV 通过调节 LDHA、p53、TIGAR、MCT1、MCT4、HIF-1α、CD147 和 miRNA-34a 的表达，缓解了异常糖酵解。
