中药治疗体外冲击波碎石失败的输尿管结石2例及网络药理学分析

Ureteral calculus treated with Chinese medicine after failure of extracorporeal shock wave lithotripsy:a report of 2 cases and network pharmacology analysis

目的 探讨成功治疗输尿管结石的方剂中主要中药及其成分的潜在机制。方法 报告2例体外冲击波碎石术(ESWL)治疗失败、经中药治疗成功排石的输尿管结石男性病例,应用网络药理学方法,分析处方中10种中药组合治疗输尿管结石的作用机制。结果 2例患者经中药治疗成功排石,复查CT未见输尿管结石及肾盂积水征象。蛋白-蛋白相互作用(PPI)网络分析发现,2例患者处方中10种中药的核心蛋白涉及ALB、MMP9、TLR4、EGF、IL-6、FN1、HSP90AA1、EGFR、AKT1、IL-10和VEGFA。京都基因与基因组百科全书(KEGG)通路富集分析发现,10种中药组合主要涉及PI3K/Akt、EGFR酪氨酸激酶抑制、TNF和HIF-1等信号通路。结论 2例ESWL治疗失败的输尿管结石经中药治疗后成功排石。网络药理学分析得出10种中药组合具有舒张输尿管平滑肌、抗炎、减少输尿管内皮损伤、利尿等作用,结石成分分析和CT值提示中药对于ESWL不敏感的输尿管结石有治疗价值。

Objective To investigate the potential mechanisms underlying the main Chinese medicines and their components in formulas for the successful treatment of ureteral calculus.Methods Two male cases of ureteral calculus who failed to undergo extracorporeal shock wave lithotripsy(ESWL)and were successfully drained by Chinese medicine treatment were reported.Network pharmacology was adapted to analyze the action mechanism of a combination of 10 Chinese herbs in prescriptions for treating ureteral calculus.Results Two men with ureteral calculus were successfully treated by Chinese medicine after the failure of ESWL,and the computer tomography(CT)reexaminations showed no ureteral calculus or hydronephrosis.Protein-protein interaction(PPI)network analysis found that the core proteins of 10 Chinese medicine herbs in the prescription involved ALB,MMP9,TLR4,EGF,IL-6,FN1,HSP90AA1,EGFR,AKT1,IL-10 and VEGFA.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway revealed that the 10 Chinese medicine herbs mainly involved PI3K/Akt,EGFR tyrosine kinase inhibition,TNF and HIF-1 signaling pathway.Conclusion Two cases of ureteral calculus with failed ESWL have been successfully drained by treatment with Chinese medicine.Network pharmacology shows that the combinations of 10 Chinese medicines have the effects of relaxing ureteral smooth muscle,anti-inflammatory,reducing ureteral endothelial damage,and diuresis.The analysis of calculus components and CT values suggests that Chinese medicine has therapeutic value for ureteral calculus,which is insensitive to ESWL.