摘要
通过联合临床疗效、代谢组学及生物信息学技术,探讨三黄护肾防衰方治疗慢性肾脏病(chronic kidney disease, CKD)的临床疗效,寻找潜在机制。收集2023年6月至2024年3月于常州市中医医院肾病科门诊或住院诊治的CKD3-4期患者,给予三黄护肾防衰方治疗,评估治疗前后疗效;同时收集治疗前后血清,基于超高效液相色谱技术检测代谢产物,采用多元统计方法进行代谢组学研究;运用生物信息学技术筛选药物活性成分靶点与CKD潜在靶点,构建交集靶点蛋白-蛋白互作(PPI)网络与药物-成分-靶点交集网络,根据网络关联度筛选核心成分与靶点,并采用分子对接进行结合效能验证。临床试验显示,三黄护肾防衰方可改善肾功能,降低蛋白尿。代谢组学分析显示,与健康人群比较,患者治疗后共54个上调代谢产物回调,43个下调代谢产物回调。富集分析显示,涉及的关键通路包括腺嘌呤核苷三磷酸结合盒(adenosine triphosphate binding cassette, ABC)转运、色氨酸代谢、酪氨酸代谢等。生物信息学显示,三黄护肾防衰方治疗CKD的核心成分包括山柰酚、β-谷甾醇、木犀草素、7-O-甲基异木果醇、丹参酮ⅡA等,核心靶点有TP53、PTGS2、JUN、AKT1、TNF。分子对接结果显示,活性成分与靶点对接结合能力好。联合通路分析结果提示,二者均涉及半乳糖代谢、烟酸烟酰胺代谢等通路。结果表明,三黄护肾防衰方能改善CKD患者肾功能,调节多个异常代谢产物,参与氨基酸、糖类等多条代谢通路;山柰酚等活性成分可能发挥了作用,干预了TP53、PTGS2等相关靶点。该研究为中医药防治CKD提供了依据。
This article aims to analyze the therapeutic effect and probe into the mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease(CKD)based on metabolomics and bioinformatics.The patients with stage 3-4 CKD diagnosed and treated in the Changzhou Hospital of Traditional Chinese Medicine from June 2023 to March 2024 were enrolled in this study.The patients were treated with Sanhuang Hushen Fangshuai Decoction,and the therapeutic effect was evaluated.The serum samples were collected before and after treatment.Ultra-performance liquid chromatography was employed to detect metabolites in the serum,and multivariate statistical analysis was performed.Bioinformatics was employed to screen the active components and targets of the decoction and the potential targets of CKD. The protein -proteininteraction network of the common targets shared by the decoction and CKD and the drug-component-target network wereconstructed. The core components and targets were screened according to the correlation degree of the network. The bindingbetween core components and targets was verified by molecular docking. The results showed that Sanhuang HushenFangshuai Decoction improved the renal function and reduced proteinuria. Compared with the healthy population, the post -treatment population showed recovery of 54 up-regulated metabolites and 43 down-regulated metabolites. Enrichment analysisresults showed that the key pathways included adenosine triphosphate binding cassette (ABC) transport, tryptophanmetabolism, and tyrosine metabolism. The results of bioinformatics analysis showed that the core components of SanhuangHushen Fangshuai Decoction in treating CKD included kaempferol, β-sitosterol, luteolin, 7-O-methylisolingol, and tanshinoneⅡA. The core targets included TP53, PTGS2, JUN, AKT1, and TNF. Molecular docking results showed that the corecomponents bound well to the target genes. The results of joint pathway analysis suggested that both differential metabolitesand key targets were involved in galactose metabolism, nicotinamide metabolism, and other pathways. This study suggeststhat Sanhuang Hushen Fangshuai Decoction is effective for CKD, and it can regulate multiple abnormal metabolites andparticipates in multiple metabolic pathways involving amino acids and sugars. The active components such as kaempferol inthe decoction may regulate related targets such as TP53 and PTGS2. This study provides a basis for the prevention andtreatment of CKD with TCM.
作者
张承华
李小艳
郑宏香
赵敏
朱美凤
闵书琪
张馨月
王身菊
ZHANG Cheng-hua;LI Xiao-yan;ZHENG Hong-xiang;ZHAO Min;ZHU Mei-feng;MIN Shu-qi;ZHANG Xin-yue;WANG Shen-ju(Changzhou Hospital of Traditional Chinese Medicine,Nanjing University of Chinese Medicine,Changzhou 213000,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2024年第23期6468-6480,共13页
China Journal of Chinese Materia Medica
基金
常州市卫健委重大科技项目(ZD202118)
江苏省中医药科技项目(YB201831)
南京中医药大学自然科学基金项目(XZR2021063)
常州首批名中医张福产传承工作室建设项目(常卫中医[2023]393号)
南京中医药大学慢性肾衰竭临床专病研究院项目(LCZBYJYZZ2024-004)。
关键词
三黄护肾防衰方
慢性肾脏病
代谢组学
生物信息学
分子对接
Sanhuang Hushen Fangshuai Decoction
chronic kidney disease
metabolomics
bioinformatics
molecular docking
