埃利安颗粒通过抑制 NF-κB 信号通路抑制肿瘤相关巨噬细胞的 M2 型极化，从而减轻大鼠胃癌前病变。
Elian granules alleviate precancerous lesions of gastric cancer in rats by suppressing M2-type polarization of tumor-associated macrophages through NF-κB signaling pathway.
机构信息
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China.
Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China.
出版信息
BMC Complement Med Ther. 2023 Jun 8;23(1):188. doi: 10.1186/s12906-023-04015-7.
BACKGROUND
Precancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats.
METHODS
The chemical ingredients of ELG were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Specific Pathogen Free SD rats were randomly assigned to 3 groups: the control, model, and ELG groups. The 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) integrated modeling method was adopted to construct the PLGC rat model in groups except for the control group. Meanwhile, normal saline was used as an intervention for the control and model groups, and ELG aqueous solution for the ELG group, lasting 40 weeks. Subsequently, the stomach of rats was harvested for further analysis. Hematoxylin-eosin staining of the gastric tissue was conducted to assess the pathological changes. Immunofluorescence was carried out for the expression of CD68, and CD206 proteins. Real-time quantitative PCR combined with Western blot was conducted to analyze the expression of arginase-1(Arg-1), inducible nitric oxide synthase (iNOS), p65, p-p65, nuclear factor inhibitor protein-α (IκBα), and p-IκBα in gastric antrum tissue.
RESULTS
Five chemical ingredients including Curcumol, Curzerenone, Berberine, Ferulic Acid, and 2-Hydroxy-3-Methylanthraquine were identified in ELG. The gastric mucosal glands of rats treated with ELG were orderly arranged, with no intestinal metaplasia and no dysplasia. Furthermore, ELG decreased the percentage of M2-type TAMs marked with CD68 and CD206 proteins, and the ratio of Arg-1 to iNOS in the gastric antrum tissue of rats with PLGC. In addition, ELG could also down-regulate the protein and mRNA expression of p-p65, p65, and p-IκBα, but up-regulate the expression of IκBα mRNA in rats with PLGC.
CONCLUSIONS
The results showed that ELG attenuates PLGC in rats by suppressing the M2-type polarization of tumor-associated macrophages (TAMs) through NF-κB signaling pathway.
背景
胃癌前病变（PLGC）是指胃黏膜的一种组织病理学改变，可进展为胃癌。连花清瘟颗粒（ELG）是一种中药方剂，在治疗 PLGC 方面取得了满意的效果。然而，ELG 的确切治疗机制尚不清楚。本研究旨在探讨 ELG 缓解大鼠 PLGC 的机制。
方法
采用超高效液相色谱-串联质谱（UPLC-MS）分析 ELG 的化学成分。将无特定病原体 SD 大鼠随机分为 3 组：对照组、模型组和 ELG 组。除对照组外，其余各组均采用 1-甲基-3-硝基-1-亚硝基胍（MNNG）整合建模法构建 PLGC 大鼠模型。同时，对照组和模型组用生理盐水干预，ELG 组用 ELG 水溶液干预，持续 40 周。然后采集大鼠胃进行进一步分析。对胃组织进行苏木精-伊红染色，评估病理变化。进行免疫荧光分析 CD68 和 CD206 蛋白的表达。实时定量 PCR 结合 Western blot 分析胃窦组织中精氨酸酶-1（Arg-1）、诱导型一氧化氮合酶（iNOS）、p65、p-p65、核因子抑制剂蛋白-α（IκBα）和 p-IκBα 的表达。
结果
ELG 中鉴定出 5 种化学成分，包括姜黄素、莪术二酮、小檗碱、阿魏酸和 2-羟基-3-甲基蒽醌。ELG 处理的大鼠胃黏膜腺体排列有序，无肠上皮化生和异型增生。此外，ELG 降低了大鼠 PLGC 胃窦组织中标记为 CD68 和 CD206 蛋白的 M2 型 TAMs 的比例，以及 Arg-1 与 iNOS 的比值。此外，ELG 还可以下调 PLGC 大鼠 p-p65、p65 和 p-IκBα 的蛋白和 mRNA 表达，但上调 IκBα 的 mRNA 表达。
结论
结果表明，ELG 通过抑制 NF-κB 信号通路抑制肿瘤相关巨噬细胞（TAMs）的 M2 型极化，从而减轻大鼠 PLGC。
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