芪芍益肾方通过色氨酸-犬尿氨酸-芳烃受体途径减轻 5/6 肾切除大鼠的肾损伤。
Bupi Yishen formula attenuates kidney injury in 5/6 nephrectomized rats via the tryptophan-kynurenic acid-aryl hydrocarbon receptor pathway.
机构信息
The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 520120, China.
Nephrology Department, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 520120, China.
出版信息
BMC Complement Med Ther. 2021 Aug 10;21(1):207. doi: 10.1186/s12906-021-03376-1.
BACKGROUND
Bupi Yishen Formula (BYF), a patent traditional Chinese medicine (TCM) formulation, has been used in the clinical treatment of chronic kidney disease (CKD). However, the mechanism of action of BYF has not been fully elucidated.
METHOD
To investigate the variation in the metabolic profile in response to BYF treatment in a rat model of 5/6 nephrectomy (Nx), rats in the treatment groups received low- or high-dose BYF. At the end of the study, serum and kidney samples were collected for biochemical, pathological, and western blotting analysis. Metabolic changes in serum were analyzed by liquid chromatography-tandem mass spectrometry.
RESULTS
The results showed that BYF treatment could reduce kidney injury, inhibit inflammation and improve renal function in a dose-dependent manner. In total, 405 and 195 metabolites were identified in negative and positive ion modes, respectively. Metabolic pathway enrichment analysis of differential metabolites based on the Kyoto Encyclopedia of Genes and Genomes database identified 35 metabolic pathways, 3 of which were related to tryptophan metabolism. High-dose BYF reduced the level of kynurenic acid (KA) by more than 50%, while increasing melatonin 25-fold and indole-3-acetic acid twofold. Expression levels of aryl hydrocarbon receptor (AhR), Cyp1A1, and CyP1B1 were significantly reduced in the kidney tissue of rats with high-dose BYF, compared to 5/6 Nx rats.
CONCLUSION
BYF has a reno-protective effect against 5/6 Nx-induced CKD, which may be mediated via inhibition of the tryptophan-KA-AhR pathway.
背景
痹祺益肾方（BYF）是一种专利的中药方剂，已用于慢性肾脏病（CKD）的临床治疗。然而，其作用机制尚未完全阐明。
方法
为了研究 BYF 治疗 5/6 肾切除（Nx）大鼠模型的代谢谱变化，治疗组大鼠给予低剂量或高剂量 BYF。研究结束时，收集血清和肾脏样本进行生化、病理和 Western blot 分析。采用液相色谱-串联质谱法分析血清代谢变化。
结果
结果表明，BYF 治疗可剂量依赖性地减轻肾脏损伤、抑制炎症和改善肾功能。在正负离子模式下分别鉴定出 405 种和 195 种代谢物。基于京都基因与基因组百科全书数据库对差异代谢物的代谢途径富集分析，共鉴定出 35 条代谢途径，其中 3 条与色氨酸代谢有关。高剂量 BYF 使犬尿氨酸（KA）的水平降低了 50%以上，同时使褪黑素增加了 25 倍，吲哚-3-乙酸增加了两倍。与 5/6 Nx 大鼠相比，高剂量 BYF 使大鼠肾脏组织中的芳香烃受体（AhR）、Cyp1A1 和 Cyp1B1 的表达水平显著降低。
结论
BYF 对 5/6 Nx 诱导的 CKD 具有肾保护作用，其机制可能是通过抑制色氨酸-KA-AhR 途径。
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