基于网络药理学和临床试验探讨健心颗粒治疗糖尿病心肌病的作用机制

Investigation of the Mechanism of Jianxin Granules in Treating Diabetic Cardiomyopathy Based on Network Pharmacology and Clinical Trials

目的:基于网络药理学和临床试验探讨健心颗粒治疗糖尿病心肌病的作用机制。方法:应用网络药理学相关工具及方法,获得健心颗粒活性成分、作用靶点及糖尿病心肌病的疾病靶点,找出健心颗粒作用于糖尿病心肌病的关键靶点,分析相关信号通路,探究可能的分子机制。通过临床试验进一步验证部分靶点,选择符合纳入标准的糖尿病心脏病患者74例,依据随机数字表随机分为治疗组和对照组,每组各37例。对照组采用常规西药治疗,治疗组在对照组基础上服用健心颗粒,观察两组超声心动图、中医症状积分的变化情况及对炎症靶点的作用。结果:共获得健心颗粒活性成分92个,药物作用靶点186个;糖尿病心肌病疾病基因780个;药物-疾病直接作用靶点91个;构建蛋白与蛋白互作(PPI)网络筛选出19个核心靶点,排名前两位为白介素-6(IL-6)、白介素-1β(IL-1β),主要通路涉及IL-17信号通路、TNF信号通路、脂质和动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路等。临床试验结果显示,健心颗粒可以改善糖尿病心肌病患者的临床症状,治疗组的中医症状积分改善情况和总有效率优于对照组(P>0.05)。两组治疗前IL-6、IL-1β、NF-κB、NT-proBNP水平比较,差异无统计学意义(P>0.05);治疗后,两组IL-6、IL-1β、NF-κB、NT-proBNP水平均较治疗前明显降低(P<0.05),且治疗组治疗后IL-6、IL-1β、NF-κB、NT-proBNP水平均低于对照组(P<0.05)。治疗组临床总有效率89.2%(33/37),高于对照组临床总有效率67.6%(25/37)(P<0.05)。结论:健心颗粒可多成分、多靶点治疗组治疗后、多通路改善糖尿病心肌病,其中通过IL-17信号通路抑制IL-6、IL-1β表达进而调节炎症反应发挥了重要作用。

Objective:To investigate the mechanism of Jianxin Granules in treating diabetic cardiomyopathy(DCM)using network pharmacology and clinical trials.Methods:Network pharmacology tools and methods were used to obtain the active components and targets of Jianxin Granules and the disease targets of DCM.Key targets of Jianxin Granules acting on DCM were identified,and relevant signaling pathways were analyzed to explore possible molecular mechanisms.Clinical trials were conducted to further validate some targets.A total of 74 patients with diabetic cardiomyopathy who met the inclusion criteria were randomly divided into a treatment group and a control group,with 37 cases in each group.The control group received conventional Western medicine treatment,while the treatment group received Jianxin Granules in addition to the treatment received by the control group.Changes in echocardiography,Traditional Chinese Medicine(TCM)symptom scores,and the effect on inflammation targets were observed in both groups.Results:A total of 92 active components and 186 drug targets of Jianxin Granules were identified;780 genes related to DCM were found;91 direct interaction targets between the drug and disease were identified;and 19 core targets were screened through the construction of a protein-protein interaction(PPI)network.The top two targets were interleukin-6(IL-6)and interleukin-1β(IL-1β),with major pathways involving the IL-17 signaling pathway,TNF signaling pathway,lipid and atherosclerosis,and the AGE-RAGE signaling pathway in diabetic complications.Clinical trial results showed that Jianxin Granules improved the clinical symptoms of DCM patients.The improvement in TCM symptom scores and the overall effectiveness rate in the treatment group were better than those in the control group(P<0.05).There was no significant difference in the levels of IL-6,IL-1β,NF-κB,and NT-proBNP between the two groups before treatment(P>0.05).After treatment,the levels of IL-6,IL-1β,NF-κB,and NT-proBNP in both groups were significantly lower than before treatment(P<0.05),and the levels in the treatment group were lower than those in the control group(P<0.05).The overall effectiveness rate was 89.2%(33/37)in the treatment group,which was higher than 67.6%(25/37)in the control group(P<0.05).Conclusion:Jianxin Granules can improve diabetic cardiomyopathy through multi-component,multi-target,and multi-pathway mechanisms.In particular,they play a significant role in regulating inflammatory responses by inhibiting IL-6 and IL-1βexpression through the IL-17 signaling pathway.