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基于依福通治疗慢性肾病患者的治疗潜力:从临床研究到基础研究

Therapeutic potential of -based Eefooton in patients with chronic kidney disease: from clinical to bench study.

作者信息

Lu Kuo-Cheng, Kuo Ko-Lin, Wu San-Chiang, Lin Chih-Hui, Lin Cheng-Ju, Hou Yi-Chou, Chen Jin-Shuen

机构信息

Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.

Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 243, Taiwan.

出版信息

Int J Med Sci. 2025 Jan 1;22(1):227-239. doi: 10.7150/ijms.102280. eCollection 2025.

Abstract

Chronic kidney disease (CKD) is a global health concern, and recent clinical evidence suggests the potential of traditional Chinese medicine (TCM) to slow CKD progression. This offers alternative strategies for CKD patients, mitigating risks related to polypharmacy and adverse drug reactions. Our self-controlled, prospective study aims to assess the impact of Eefooton (EFT), a TCM-based regimen, on kidney health in stage 3-5 CKD patients. Additionally, we conduct a cell culture study to explore the potential mechanisms of EFT in protecting renal function. Between 2021 and 2022, 75 stage 3-5 CKD patients (56% males; mean age 68.20y) at Kaohsiung Veterans General Hospital and Wu San-Chiang Medical Clinic received six months of EFT treatment alongside conventional CKD medications. The primary outcome assessed was the change in estimated glomerular filtration rate (eGFR) at 6 months, with secondary outcomes including kidney size and blood biomarker changes. Adverse events were monitored. In an study, EFT effects on HK-2 cell viability and clonogenicity, as well as analysis of apoptosis and fibrosis-related proteins through Western blot, were investigated. Median eGFR significantly improved from 34.37 ± 13.58 to 42.47 ± 18.82 mL/min/1.73 m (p < 0.001) at month 6 post-treatment. Notably, improvements were observed across different baseline CKD stages (stage 3: p < 0.001, stage 4: p = 0.037). Ultrasonography scans indicated a slight increase in mean kidney size. , EFT enhanced HK-2 cell viability and increased clonogenicity. Indoxyl sulfate exposure raised cleaved and total PARP-1 activity. Co-treatment with EFT and IS reduced cleaved PARP-1 activity. EFT decreased IS-induced expression of fibrosis-related proteins (α-smooth muscle actin) without affecting apoptosis-related proteins (Caspase 3). When combined with conventional CKD medications, EFT has shown effectiveness in enhancing kidney function in individuals with stage 3-5 CKD, with no reported safety concerns. The PARP-1 inhibition and anti-fibrosis properties of EFT present potential benefits in the context of CKD.

摘要

慢性肾脏病(CKD)是一个全球性的健康问题,最近的临床证据表明,中医药(TCM)具有减缓CKD进展的潜力。这为CKD患者提供了替代策略,降低了与多药联用及药物不良反应相关的风险。我们的自我对照前瞻性研究旨在评估基于中医的益方通(EFT)方案对3-5期CKD患者肾脏健康的影响。此外,我们进行了细胞培养研究,以探索EFT保护肾功能的潜在机制。2021年至2022年期间,高雄荣民总医院和吴三江诊所的75例3-5期CKD患者(56%为男性;平均年龄68.20岁)在接受常规CKD药物治疗的同时接受了6个月的EFT治疗。评估的主要结局是6个月时估计肾小球滤过率(eGFR)的变化,次要结局包括肾脏大小和血液生物标志物变化。对不良事件进行了监测。在一项研究中,研究了EFT对HK-2细胞活力和克隆形成能力的影响,以及通过蛋白质印迹法分析凋亡和纤维化相关蛋白。治疗后第6个月,eGFR中位数从34.37±13.58显著提高至42.47±18.82 mL/min/1.73 m²(p<0.001)。值得注意的是,在不同的基线CKD阶段均观察到改善(3期:p<0.001,4期:p=0.037)。超声扫描显示平均肾脏大小略有增加。此外,EFT增强了HK-2细胞活力并增加了克隆形成能力。硫酸吲哚酚暴露增加了裂解型和总PARP-1活性。EFT与硫酸吲哚酚联合处理降低了裂解型PARP-1活性。EFT降低了硫酸吲哚酚诱导的纤维化相关蛋白(α-平滑肌肌动蛋白)的表达,而不影响凋亡相关蛋白(半胱天冬酶3)。当与常规CKD药物联用时,EFT已显示出对3-5期CKD患者增强肾功能有效,且未报告安全问题。EFT的PARP-1抑制和抗纤维化特性在CKD背景下具有潜在益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e3/11659832/bb75c412789b/ijmsv22p0227g001.jpg

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