Liu Xinhui, Deng Ruyu, Chen Yulian, Huang Shiying, Lu Jiandong, Zheng Lin, Xiong Guoliang, Li Shunmin
Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China.
Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, China.
Front Pharmacol. 2022 Jul 5;13:922707. doi: 10.3389/fphar.2022.922707. eCollection 2022.
Traditional Chinese medicine (TCM) is an important complementary and alternative branch of chronic kidney disease (CKD) therapy. Jian-Pi-Yi-Shen formula (JPYSF) is a TCM formula used for treating CKD with good efficacy. However, the underlying mechanisms of JPYSF in treating CKD remain to be elucidated. The purpose of the present study was to investigate the renoprotective effect and potential mechanism of JPYSF in treating CKD. CKD rat model was induced by feeding a diet containing 0.75% w/w adenine for 4 weeks. JPYSF was given by gavage every day, starting from the 3rd week of the adenine-containing diet and continuing for 4 weeks at the dose of 10.89 g/kg. Renal injury was evaluated by serum creatinine (Scr), blood urea nitrogen (BUN), histopathology, and fibrotic markers expression. Serum levels of tryptophan metabolites were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Aryl hydrocarbon receptor (AHR) signaling was tested by Western blot analysis. The results found that JPYSF treatment significantly lowered Scr and BUN levels, improved renal pathological injury, and down-regulated fibrotic markers expression in CKD rats. Furthermore, JPYSF significantly reduced the levels of 10 tryptophan metabolites in the serum of CKD rats and restored the level of tryptophan. Additionally, the kidney expression of AHR signaling was enhanced in CKD rats and was further suppressed in JPYSF treated rats. These results suggested that JPYSF protected against adenine-induced CKD via modulating tryptophan metabolism and AHR activation.
传统中医（TCM）是慢性肾脏病（CKD）治疗中一个重要的补充和替代医学分支。健脾益肾方（JPYSF）是一种用于治疗CKD且疗效良好的中药方剂。然而，JPYSF治疗CKD的潜在机制仍有待阐明。本研究的目的是探讨JPYSF治疗CKD的肾脏保护作用及其潜在机制。通过喂食含0.75% w/w腺嘌呤的饮食4周诱导建立CKD大鼠模型。从给予含腺嘌呤饮食的第3周开始，每天通过灌胃给予JPYSF，持续4周，剂量为10.89 g/kg。通过血清肌酐（Scr）、血尿素氮（BUN）、组织病理学和纤维化标志物表达评估肾脏损伤。采用超高效液相色谱-串联质谱（UHPLC-MS/MS）检测血清中色氨酸代谢产物水平。通过蛋白质免疫印迹分析检测芳烃受体（AHR）信号通路。结果发现，JPYSF治疗显著降低了CKD大鼠的Scr和BUN水平，改善了肾脏病理损伤，并下调了纤维化标志物的表达。此外，JPYSF显著降低了CKD大鼠血清中10种色氨酸代谢产物的水平，并恢复了色氨酸水平。此外，CKD大鼠肾脏中AHR信号通路的表达增强，而JPYSF治疗的大鼠中该通路进一步受到抑制。这些结果表明，JPYSF通过调节色氨酸代谢和AHR激活来保护腺嘌呤诱导的CKD。
