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基于网络药理学探讨艾莲颗粒通过 MAPK 信号通路治疗胃癌前病变大鼠的作用机制。

Mechanism of Elian granules in the treatment of precancerous lesions of gastric cancer in rats through the MAPK signalling pathway based on network pharmacology.

机构信息

The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, People's Republic of China.

Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

出版信息

Pharm Biol. 2022 Dec;60(1):87-95. doi: 10.1080/13880209.2021.2017980.

Abstract

CONTEXT

Elian Granules have been applied in the treatment of precancerous lesions of gastric cancer (PLGC) and achieved good results. However, its exact mechanism remains unclear.

OBJECTIVES

To explore the mechanism of Elian granules in treating PLGC through the mitogen-activated protein kinase (MAPK) signalling pathway based on network pharmacology.

MATERIALS AND METHODS

Through network pharmacological methods, the targets of the active component of Elian granules against PLGC were obtained. Subsequently, Specific Pathogen Free (SPF) male Sprague Dawley (SD) rats were randomly divided into normal, model, and Elian granule groups. The -methyl-'-nitro--nitrosoguanidine comprehensive method was used to establish the PLGC rat model. The model and Elian granule groups were given normal saline and Elian granule aqueous solution (3.24 g/kg/d) intragastric administration, respectively, for 24 weeks. The pathological changes in gastric tissues were observed by hematoxylin-eosin staining. The protein expression of p-JNK and p-p38 was verified by western blotting.

RESULTS

394 and 4,395 targets were identified in Elian granules and PLGC, respectively. The 190 common targets were mainly enriched in MAPK signalling pathways. The gastric mucosal epithelium was still intact, the glands were arranged regularly, and no goblet cells or apparent inflammatory cell infiltration were observed in the Elian granule group. The expression of p-JNK and p-p38 protein of the Elian granule group (0.83 ± 0.08; 1.18 ± 0.40) was significantly higher than the model group (0.27 ± 0.14; 0.63 ± 0.14) ( < 0.01;  < 0.05).

DISCUSSION AND CONCLUSIONS

Elian granules may play a critical role in the treatment of rat PLGC by up-regulating the expression of p-JNK and p-p38 proteins in the MAPK signalling pathway, thus providing a scientific basis for clinical application.

摘要

背景

以莲芪颗粒治疗胃癌前病变(PLGC)取得了良好的效果。但其确切机制尚不清楚。

目的

基于网络药理学探讨莲芪颗粒通过丝裂原活化蛋白激酶(MAPK)信号通路治疗 PLGC 的作用机制。

材料与方法

采用网络药理学方法获得莲芪颗粒治疗 PLGC 的活性成分作用靶点。随后,将 SPF 雄性 SD 大鼠随机分为正常组、模型组和莲芪颗粒组。采用甲基硝基亚硝基胍综合法建立 PLGC 大鼠模型。模型组和莲芪颗粒组分别给予生理盐水和莲芪颗粒水溶液(3.24g/kg/d)灌胃,连续 24 周。苏木精-伊红染色观察胃组织病理变化,Western blot 法验证胃组织中 p-JNK 和 p-p38 蛋白的表达。

结果

莲芪颗粒和 PLGC 分别鉴定出 394 个和 4395 个靶标,190 个共有靶标主要富集在 MAPK 信号通路中。莲芪颗粒组胃黏膜上皮完整,腺体排列规则,未见杯状细胞或明显炎症细胞浸润。与模型组比较,莲芪颗粒组 p-JNK 和 p-p38 蛋白表达(0.83±0.08;1.18±0.40)升高( < 0.01; < 0.05)。

讨论与结论

莲芪颗粒可能通过上调 MAPK 信号通路中 p-JNK 和 p-p38 蛋白的表达,发挥治疗大鼠 PLGC 的作用,为临床应用提供科学依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c14/8725869/6cf1864cffbc/IPHB_A_2017980_F0001_C.jpg

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