姜附复萎颗粒治疗脾肾阳虚型慢性萎缩性胃炎的药理作用机制研究  

Pharmacological Mechanism of Jiangfu Fuwei Granules in the Treatment of ChronicAtrophic Gastritis with Spleen and Kidney Yang Deficiency Syndrome

作　　者：尤旭颖 蔡悦青 张月林 王坤宁 白亚丽 景燕燕 姜莉云[2] 袁红霞[1] YOU Xuying;CAI Yueqing;ZHANG Yuelin;WANG Kunning;BAI Yali;JING Yanyan;JIANG Liyun;YUAN Hongxia(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Kunming Municipal Hospital of Traditional Chinese Medicine,Kunming 650011,China)

机构地区：[1]天津中医药大学,天津301617 [2]昆明市中医医院,昆明650011

出　　处：《世界中医药》2025年第2期189-197,共9页World Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(82204962);云南省万人计划-名医专项(YNWR-MY-2018-057);云南省科技厅科技计划项目基础研究计划中医联合专项-青年项目(202001AZ070001-099);天津市卫生健康委员会天津市中医药重点领域科研项目(2021006);天津市教委社会科学重大项目(2021JWZD23)。

摘　　要：目的:基于网络药理学和分子对接技术结合体内实验验证,探讨姜附复萎颗粒(JFFW)治疗脾肾阳虚型慢性萎缩性胃炎(CAG)的作用机制。方法:采用网络药理学和分子对接技术预测JFFW干预CAG的潜在靶点,再利用动物实验进行验证。将SPF级SD雄性大鼠50只按照随机数字表法分为空白组(10只)和造模大鼠(40只)。造模组大鼠使用N-甲基-N′-硝基-N-亚硝基胍(MNNG)+生大黄颗粒+隔日禁食法来诱导模型,造模成功后,按照随机数字表法分为模型组、西药组、中药组,每组10只,分别予以蒸馏水、叶酸片+瑞巴派特片、JFFW灌胃治疗,为期12周。之后,通过苏木精-伊红(HE)染色、酶联免疫吸附测定、实时PCR和蛋白质印迹法等方法进行相关指标检测。结果:网络药理学及分子对接结果均表明肿瘤坏死因子(TNF)、胱天蛋白酶3(Caspase3)、胱天蛋白酶8(Caspase8)是JFFW干预CAG的核心靶点;实验结果表明,JFFW可以显著改善大鼠胃黏膜病理情况,显著升高CAG大鼠血清中胃泌素17(GAS-17)、胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅰ与胃蛋白酶原Ⅱ的比值(PGⅠ/PGⅡ)的表达(P<0.05),显著下调CAG大鼠胃组织人肿瘤坏死因子α(TNF-α)、肿瘤坏死因子受体1(TNFR1)、肿瘤坏死因子受体相关死亡结构域蛋白(TRADD)的mRNA及蛋白表达,上调死亡结构域相关蛋白(FADD)、Caspase8、Caspase3的mRNA及蛋白表达(P<0.05)。结论:JFFW通过调控TNF信号通路,减轻炎症反应,促进细胞的凋亡,发挥抗肿瘤效应,从而缓解或逆转CAG病情。Objective:To explore the mechanism of Jiangfu Fuwei Granules(JFFW)in treating chronic atrophic gastritis(CAG)of spleen-kidney yang deficiency type based on network pharmacology,molecular docking,and in vivo experimental validation.Methods:Network pharmacology and molecular docking techniques were employed to predict the potential targets of JFFW in CAG intervention,followed by validation through animal experiments.Fifty SPF-grade male SD rats were randomly divided into a blank group(n=10)and a modeling group(n=40).The CAG model was induced in the modeling group using N-methyl-N′-nitro-N-nitrosoguanidine(MNNG),Shengdahuang Granules,and intermittent fasting.After successful modeling,the rats were randomly assigned into three groups:model group,Western medicine group,and Chinese medicine group according to a random number table,with 10 rats in each group.They were administered distilled water,folic acid tablets+rebamipide tablets,or JFFW by gavage for 12 weeks.Hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),real-time PCR,and Western blot were used to assess relevant indicators.Results:Network pharmacology and molecular docking analysis identified tumor necrosis factor(TNF),Caspase-3,and Caspase-8 as core targets of JFFW in CAG intervention.Experimental results demonstrated that JFFW significantly improved gastric mucosal pathology and increased serum levels of gastrin-17(GAS-17),pepsinogenⅠ(PGⅠ),and the PGⅠ/PGⅡratio in CAG rats(P<0.05).Furthermore,JFFW significantly downregulated mRNA and protein expression of tumor necrosis factor-alpha(TNF-α),tumor necrosis factor receptor 1(TNFR1),and TNF receptor-associated death domain protein(TRADD)in gastric tissues while upregulating the expression of Fas-associated death domain protein(FADD),Caspase-8,and Caspase-3(P<0.05).Conclusion:JFFW alleviates or reverses CAG by regulating the TNF signaling pathway,reducing inflammation,and promoting apoptosis,thereby exerting anti-tumor effects.

关 键 词：网络药理学 分子对接 慢性萎缩性胃炎 姜附复萎颗粒 TNF信号通路 扶阳流派 升举三阴法 机制研究 

分 类 号：R289[医药卫生—方剂学] R285[医药卫生—中药学] R228[医药卫生—中医学] R256