Liu Meifang, Di Yuan Ming, May Brian, Zhang Anthony Lin, Zhang Lei, Chen Junhui, Wang Ruobing, Liu Xusheng, Xue Charlie Changli
China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, RMIT University, Melbourne, 3083, Australia; Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120, China.
China-Australia International Research Centre for Chinese Medicine, School of Health and Biomedical Sciences, RMIT University, Melbourne, 3083, Australia.
Phytomedicine. 2024 Jul;129:155646. doi: 10.1016/j.phymed.2024.155646. Epub 2024 Apr 27.
Astragalus membranaceus (AM) shows potential therapeutic benefits for managing diabetic kidney disease (DKD), a leading cause of kidney failure with no cure. However, its comprehensive effects on renal outcomes and plausible mechanisms remain unclear.
This systematic review and meta-analysis aimed to synthesize the effects and mechanisms of AM on renal outcomes in DKD animal models.
Seven electronic databases were searched for animal studies until September 2023. Risk of bias was assessed based on SYRCLE's Risk of Bias tool. Standardized mean difference (SMD) or mean difference (MD) were estimated for the effects of AM on serum creatinine (SCr), blood urea nitrogen (BUN), albuminuria, histological changes, oxidative stress, inflammation, fibrosis and glucolipids. Effects were pooled using random-effects models. Heterogeneity was presented as I. Subgroup analysis investigated treatment- and animal-related factors for renal outcomes. Publication bias was assessed using funnel plots and Egger's test. Sensitivity analysis was performed to assess the results' robustness. RevMan 5.3 and Stata MP 15 software were used for statistical analysis.
Forty studies involving 1543 animals were identified for analysis. AM treatment significantly decreased SCr (MD = -19.12 μmol/l, 95 % CI: -25.02 to -13.23), BUN (MD = -6.72 mmol/l, 95 % CI: -9.32 to -4.12), urinary albumin excretion rate (SMD = -2.74, 95 % CI: -3.57, -1.90), histological changes (SMD = -2.25, 95 % CI: -3.19 to -1.32). AM treatment significantly improved anti-oxidative stress expression (SMD = 1.69, 95 % CI: 0.97 to 2.41), and decreased inflammation biomarkers (SMD = -3.58, 95 % CI: -5.21 to -1.95). AM treatment also decreased fibrosis markers (i.e. TGF-β1, CTGF, collagen IV, Wnt4 and β-catenin) and increased anti-fibrosis marker BMP-7. Blood glucose, lipids and kidney size were also improved compared with the DM control group.
AM could improve renal outcomes and alleviate injury through multiple signaling pathways. This indicates AM may be an option to consider for the development of future DKD therapeutics.
黄芪对治疗糖尿病肾病（DKD）具有潜在的治疗益处，糖尿病肾病是肾衰竭的主要原因且无法治愈。然而，其对肾脏结局的综合影响及可能的机制仍不清楚。
本系统评价和荟萃分析旨在综合黄芪对DKD动物模型肾脏结局的影响及机制。
检索七个电子数据库以查找截至2023年9月的动物研究。基于SYRCLE的偏倚风险工具评估偏倚风险。估计黄芪对血清肌酐（SCr）、血尿素氮（BUN）、蛋白尿、组织学变化、氧化应激、炎症、纤维化和糖脂的影响的标准化均数差（SMD）或均数差（MD）。使用随机效应模型汇总效应。异质性以I²表示。亚组分析研究了与肾脏结局相关的治疗和动物因素。使用漏斗图和Egger检验评估发表偏倚。进行敏感性分析以评估结果的稳健性。使用RevMan 5.3和Stata MP 15软件进行统计分析。
确定40项涉及1543只动物的研究进行分析。黄芪治疗显著降低了SCr（MD = -19.12 μmol/l，95%CI：-25.02至-13.23）、BUN（MD = -6.72 mmol/l，95%CI：-9.32至-4.12）、尿白蛋白排泄率（SMD = -2.74，95%CI：-3.57，-1.90）、组织学变化（SMD = -2.25，95%CI：-3.19至-1.32）。黄芪治疗显著改善了抗氧化应激表达（SMD = 1.69，95%CI：从0.97至2.41），并降低了炎症生物标志物（SMD = -3.58, 95%CI：-5.21至-1.95）。黄芪治疗还降低了纤维化标志物（即TGF-β1、CTGF、IV型胶原、Wnt4和β-连环蛋白），并增加了抗纤维化标志物BMP-7。与糖尿病对照组相比，血糖、血脂和肾脏大小也得到改善。
黄芪可通过多种信号通路改善肾脏结局并减轻损伤。这表明黄芪可能是未来DKD治疗药物开发中可考虑的一种选择。
