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加味七方胃痛颗粒改善胃癌前病变的作用机制预测与验证
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| 篇名： | 加味七方胃痛颗粒改善胃癌前病变的作用机制预测与验证 |
| TITLE： | Prediction and verification of the mechanism of action of Jiawei qifang weitong granule in ameliorating precancerous lesions of gastric cancer |
| 摘要： | 目的 预测并验证加味七方胃痛颗粒改善胃癌前病变（PLGC）的作用机制。方法通过GEO数据库获取PLGC相关转录组学数据，筛选差异表达基因并进行功能富集分析；结合GeneCards数据库筛选胃黏膜损伤修复靶点；借助TCMSP等数据库预测加味七方胃痛颗粒活性成分作用靶点；将差异表达基因、胃黏膜修复靶点、活性成分作用靶点取交集后，基于STRING数据库构建蛋白互作网络并筛选连接度排名前6位的关键靶点基因。采用1-甲基-3-硝基-1-亚硝基胍联合“饥饿-饱腹交替”法构建PLGC大鼠模型，然后分为模型组、胃复春组（阳性对照，0.40g/kg）和加味七方胃痛颗粒低、中、高剂量组（9.73、19.44、38.90g/kg），每组10只；另将10只未建模大鼠作为对照组。各组大鼠灌胃相应药液/生理盐水，每天1次，连续30d。末次给药后，观察大鼠胃组织病理形态学变化，检测大鼠胃组织中关键靶点基因mRNA和部分蛋白表达水平。结果转录组学和网络药理学分析结果显示，连接度排名前6位的关键靶点基因包括MMP9（基质金属蛋白酶9）、BCL2（B细胞淋巴瘤2）、IL10（白细胞介素10）、ICAM1（细胞间黏附分子1）、PTGS2（前列腺素内过氧化物合酶2）、HIF1A（缺氧诱导因子1α亚基）。动物实验结果显示，与模型组比较，加味七方胃痛颗粒中、高剂量组和胃复春组大鼠胃黏膜病理损伤明显减轻，胃黏膜病理损伤评分和胃组织中MMP9、PTGS2、ICAM1、BCL2、HIF1AmRNA的表达水平以及PTGS2、BCL2蛋白表达水平均显著降低（P＜0.05），IL10mRNA的表达水平均显著升高（P＜0.05）。结论加味七方胃痛颗粒可能通过靶向下调MMP9、PTGS2、ICAM1、BCL2、HIF1AmRNA表达，上调IL10mRNA表达，调节胃黏膜炎症反应与损伤修复失衡状态，从而改善PLGC。 |
| ABSTRACT： | Abstract OBJECTIVE To predict and verify the mechanism of Jiawei qifang weitong granule in ameliorating precancerous lesions of gastric cancer （PLGC）. METHODS Transcriptomic data of PLGC-related were obtained from the GEO database to screen differentially expressed genes and conduct functional enrichment analysis. Targets related to gastric mucosal injury repair were screened via the GeneCards database. The active ingredient targets of Jiawei qifang weitong granule were predicted using the TCMSP and other databases. The intersection of differentially expressed genes， gastric mucosal repair targets and active ingredient targets was extracted. A protein-protein interaction network was constructed based on the STRING database， and the top 6 hub target genes with the highest connectivity were screened. A PLGC rat model was established by combining 1-methyl-3-nitro-1-nitrosoguanidine with alternating fasting and full feeding. Model rats were divided into model group， weifuchun group （positive control， 0.40 g/kg）， low-， medium- and high-dose Jiawei qifang weitong granule groups （9.73， 19.44， 38.90 g/kg）， with 10 rats in each group. Another 10 unmodeled rats were set as control group. Rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 30 consecutive days. After the last administration， pathological morphological changes of rat gastric tissues were observed， and the mRNA expression levels of hub target genes as well as partial protein expression levels in gastric tissues were detected. RESULTS Transcriptomics and network pharmacology analyses revealed that the top 6 hub target genes ranked by connectivity included MMP9 （matrix metalloproteinase 9）， BCL2（B-cell lymphoma 2）， IL10（interleukin 10），ICAM1（intercellular adhesion molecule 1）， PTGS2 （prostaglandin-endoperoxide synthase 2）， and HIF1A （hypoxia-inducible factor 1α subunit）. Animal experiments showed that compared with the model group， gastric mucosal pathological injury was significantly alleviated in medium- and high-dose Jiawei qifang weitong granule groups and weifuchun group. The pathological injury score of gastric mucosa， the mRNA expression levels of MMP9， PTGS2， ICAM1， BCL2 and HIF1A， as well as the protein expression levels of PTGS2 and BCL2 in gastric tissues were significantly decreased （P＜0.05）， while the mRNA expression level of IL10 was significantly increased （P＜0.05）. CONCLUSIONS Jiawei qifang weitong granule may ameliorate PLGC by targeted down-regulating the mRNA expression of MMP9， PTGS2， ICAM1， BCL2 and HIF1A， up-regulating IL10 mRNA expression， and regulating the imbalance between gastric mucosal inflammatory response and injury repair. |
| 期刊： | 2026年第37卷第15期 |
| 作者： | 陈文隆；唐梅文；于业平；陈鑫源；庞龙；熊常州；梁英业；王婷 |
| AUTHORS： | CHEN Wenlong， TANG Meiwen，YU Yeping，CHEN Xinyuan，PANG Long，XIONG Changzhou，LIANG Yingye，WANG Ting |
| 关键字： | 加味七方胃痛颗粒；胃癌前病变；胃黏膜损伤；网络药理学；转录组学 |
| KEYWORDS： | Jiawei qifang weitong granule； precancerous lesions of gastric cancer； gastric mucosal injury； network pharmacology； transcriptomics |
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