The gastric mucosal protective effects of astragaloside IV in mnng-induced GPL rats
The gastric mucosal protective effects of astragaloside IV in mnng-induced GPL rats
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黄芪甲苷IV对mnng诱导的GPL大鼠胃黏膜的保护作用
DOI：
10.1016/j.biopha.2018.04.013
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发表时间：
2018-08-01
影响因子：
7.5
通讯作者：
Zeng, Xiaohui
中科院分区：
文献类型：
--
作者：
Cai, Tiantian;Zhang, Chengzhe;Zeng, Xiaohui
胃癌是最常见的癌症类型之一。胃癌的发生是一个进化的组织病理阶段。因此，进一步研究作为胃癌边缘的GPL对于预防胃癌的形成和发展是必不可少的。多项研究表明，自噬、细胞凋亡的表达与胃癌（GC）之间存在相关性。然而，自噬和凋亡对人类胃癌进展的影响，特别是对胃癌前病变（GPL）的影响尚未完全研究。黄芪甲苷（Astragaloside IV, AS-IV）是一种从黄芪中纯化的皂苷，黄芪是一种中药，2000多年来被广泛用于治疗癌症、心血管和免疫疾病。本实验旨在探讨AS-IV对n -甲基-n '-硝基-n -亚硝基胍（MNNG）诱导的GPL大鼠胃黏膜的保护作用机制。与模型大鼠相比，GIM和GED的病变明显改善，尤其是拥挤的管状腺和背对背的管状结构，这是GPL和GC的危险分界线。Western Blot分析显示，AS-IV组与模型组比较，Bcl-2/Bax比值及Bcl-XL、p53、Beclin1、p62、ATG5、ATG12蛋白表达降低，Caspase3水平升高；RT-PCR分析显示，AS-IV组与模型组比较，Ambra1、Beclin1、ATG5、LC3、p62基因表达降低。本研究表明胃癌发生前有较长的癌前期，AS-IV可改善癌前期。同时，轻、中度癌前病变在炎症、细胞增殖、分化等关键生物学过程上与胃腺癌相似。但这种病变与癌症有很大的不同，因为它在这个病理阶段不会出现明显的侵袭性和恶性病变。AS-IV可调节p53表达，激活GPL中Ambra1/Beclin1复合物，保护胃黏膜损伤，防治胃黏膜萎缩、肠化生和不典型增生性病变。为逆转GPL大鼠肠化生和胃癌前病变不典型增生及保护胃黏膜提供了潜在的治疗策略。
Gastric Cancer is one of the most common types of cancer. And the occurrence of gastric carcinoma is an evolutionary histopathological stage. As a result, further research of GPL, which is a borderline of gastric cancer, is indispensable for preventing the formation and development of gastric carcinoma. Several studies have demonstrated a correlation between the expression of autophagy, apoptosis and Gastric cancer (GC). However, the effects of autophagy and apoptosis on human gastric cancer progression, particularly on gastric precancerous lesions (GPL), have not totally been investigated. At present, Astragaloside IV(AS-IV) is a saponin purified from Astragalus membranaceous Bge, a traditional Chinese herb that has been widely used for more than 2000 y in the treatment of cancer, cardiovascular and immune disorders. This study was designed to investigate the mechanism of AS-IV protecting gastric mucosa in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL rats. The lesions of GIM and GED were significantly ameliorated compared with the model rats, especially crowded tubular glandular and back-to-back tubular structure, which were the dangerous borderline between GPL and GC. Western Blot analysis showed that the ratio of Bcl-2/Bax and the protein expression of Bcl-XL, p53, Beclin1, p62, ATG5 and ATG12 were decreased and the level of Caspase3 was increased in the group of AS-IV compared with the model group; RT-PCR analysis showed that the gene expression Ambra1, Beclin1, ATG5, LC3 and p62 were decreased in the group of AS-IV compared with the model group. This research manifested that the occurrence of gastric cancer was preceded by a prolonged precancerous stage, which could be ameliorated by the AS-IV. Meanwhile, the mild and moderate stage of precancerous lesions is similar with gastric adenocarcinoma in critical biological processes, including inflammation, cell proliferation, differentiation. But this lesion is very different from cancer, because it does not appear obvious invasion and malignant lesions in this pathologic stag. Further, AS-IV could regulate p53 expression to activate the Ambra1/Beclin1 complex in GPL, and it will protect the gastric mucosal injury, prevent and cure gastric mucosal atrophy, intestinal metaplasia and atypical hyperplastic lesions. It provided a potential therapeutic strategy in reversing intestinal metaplasia and dysplasia of gastric precancerous lesions and protecting the gastric mucosa in GPL rats.