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目的:采用网络药理学及病证结合理论探讨加味附子理中汤治疗阳虚型溃疡性结肠炎(UC)的作用机制，并进行实验验证。方法:基于网络药理学预测得到加味附子理中汤治疗阳虚型UC的核心成分、作用靶点和主要通路；利用GEO数据库对作用靶点进行差异验证；采用大黄煎剂合并2,4,6-三硝基苯磺酸5%水溶液(TNBS)-乙醇复合法诱导阳虚型UC大鼠模型，观察加味附子理中汤对阳虚型UC大鼠的影响，进一步验证其作用机制。结果:通过网络药理学分析，加味附子理中汤的核心成分主要包括槲皮素、汉黄芩素、木犀草素、异鼠李素、等，关键靶点包括AKT1、IL-6、VEGFA、CASP3、IL-4、等，可能通过PI3K-AKT信号通路、MAPK信号通路、TNF信号通路等发挥治疗阳虚型UC的作用。在动物试验方面，与模型对照组比较，加味附子理中汤20 g/kg组能有效改善阳虚型UC模型大鼠结肠病理情况，降低血清促炎因子IL-6含量，升高抑炎因子IL-4含量，下调结肠PI3K、AKT、NF-κB蛋白表达。结论:加味附子理中汤可能通过调控PI3K-AKT信号通路相关蛋白的表达及IL-4、IL-6、等炎症因子的释放发挥治疗阳虚型UC的作用。
Abstract：Objective:To explore the mechanism of Jiawei Fuzi Lizhong Decoction(加味附子理中汤) in the treatment of ulcerative colitis(UC) with Yangxu(阳虚) through network pharmacology combined with disease-syndrome combination theory based on experimental verification. Methods:The core components, targets, and key pathways of Jiawei Fuzi Lizhong Decoction in the treatment of UC with Yangxu were obtained based on the network pharmacology prediction. Gene Expression Omnibus(GEO) database was used to verify the differences in the core targets. The UC model with Yangxu was induced in rats by Dahuang(大黄) Decoction combined with 5% 2,4,6-trinitrobenzene sulfonic acid(TNBS) solution-ethanol. The effect of Jiawei Fuzi Lizhong Decoction on UC rats with Yangxu was observed to further verify its mechanism. Results:As revealed by network pharmacology analysis, the active components of Jiawei Fuzi Lizhong Decoction mainly included quercetin, wogonin, luteolin, and isorhamnetin, and the core targets included AKT1,IL-6,VEGFA,CASP3,IL-4. In addition, Jiawei Fuzi Lizhong Decoction presumedly played a therapeutic role on UC with Yangxu through the PI3 K-Akt signaling pathway, the MAPK signaling pathway, and the TNF signaling pathway. As demonstrated by the animal experiment, compared with the model group, Jiawei Fuzi Lizhong Decoction(20 g/kg) could effectively improve the colonic pathology of UC rats, reduce the level of serum pro-inflammatory factor IL-6,increase the level of anti-inflammatory factor IL-4,and down-regulate the expression of PI3 K,Akt, and NF-κB. Conclusion:Jiawei Fuzi Lizhong Decoction may treat UC with Yangxu by regulating the expression of related proteins on the PI3 K-Akt signaling pathway and the release of inflammatory factors, such as IL-4 and IL-6.
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基本信息:
DOI：10.13412/j.cnki.zyyl.20220419.003
中图分类号:R285.5
引用信息:
[1]刘青松,郝彦伟,张怡,等.基于网络药理学和实验验证探讨加味附子理中汤治疗阳虚型溃疡性结肠炎的作用机制[J].中药药理与临床,2022,38(05):32-38.DOI:10.13412/j.cnki.zyyl.20220419.003.
基金信息:
国家自然科学基金面上项目(编号：81973821)
2022-04-20
2022-04-20
2022-04-20