Lu Lingfei, Lu Jiandong, Chen Jiwei, Wang Bing, Peng Hongcheng, Peng Jinting, Liu Xinhui, Lin Feng, Xiong Guoliang
Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.
Front Pharmacol. 2023 Apr 6;14:1103527. doi: 10.3389/fphar.2023.1103527. eCollection 2023.
Chronic kidney disease (CKD) is usually insidious, and most affected individuals are asymptomatic until the disease becomes advanced. The effective treatment of CKD would rely on the incorporation of multidisciplinary approaches. (AM) and (CZ) have been widely used in the treatment of CKD. However, the mechanism of AM and CZ in the treatment of CKD is still unclear. This study was designed to evaluate the effects of AM and CZ on adenine-induced rats and to investigate the underlying mechanism by using metabolomic analysis. Addition of 0.75% adenine to the diet of rats for 3 weeks induced the animal model of CKD. The rats in the treatment group were treated with AM and CZ (2.1 g/kg/day) for 4 weeks. Blood and kidney samples were collected for biochemical and histological examination. Ultra-high-performance liquid chromatography/Q Exactive HFX mass spectrometer (UHPLC-QE-MS) was applied to analyze metabolic profiling variations in the kidney. The results showed that AM and CZ could significantly reduce serum creatinine (Scr) and blood urea nitrogen (BUN) levels in CKD rats and alleviate renal pathological injury. By comparing the endogenous components of the normal group and the model group in positive ion mode and negative ion mode, a total of 365 and 155 different metabolites were screened, respectively. A total of 117 and 73 metabolites with significantly different expressions were identified between model group and AM and CZ group in positive ion mode and negative ion mode, respectively. The pivotal pathways affected by AM and CZ included nicotinate and nicotinamide metabolism, and glycine, serine and threonine metabolism. Furthermore, significant changes in metabolites in CKD rats after AM and CZ therapies were observed, including L-Threonine, D-pantothenic acid, and nicotinamide. Moreover, we found that AM and CZ significantly reduced renal fibrosis and inflammation in CKD rats, which may be related to the regulation of SIRT1/JNK signaling pathway. In conclusion, AM and CZ significantly reduced renal fibrosis and inflammation in CKD rats, which may be related to the regulation of SIRT1/JNK signaling pathway. Furthermore, L-Threonine, D-pantothenic acid, and nicotinamide may be potential biomarkers for the progression and treatment of CKD.
慢性肾脏病（CKD）通常隐匿起病，大多数患者在疾病进展之前没有症状。CKD的有效治疗依赖于多学科方法的整合。黄芪甲苷（AM）和积雪草苷（CZ）已广泛用于CKD的治疗。然而，AM和CZ治疗CKD的机制仍不清楚。本研究旨在评估AM和CZ对腺嘌呤诱导大鼠的影响，并通过代谢组学分析探究其潜在机制。在大鼠饮食中添加0.75%腺嘌呤3周诱导建立CKD动物模型。治疗组大鼠用AM和CZ（2.1 g/kg/天）治疗4周。采集血液和肾脏样本进行生化和组织学检查。应用超高效液相色谱/Q Exactive HFX质谱仪（UHPLC-QE-MS）分析肾脏中的代谢谱变化。结果表明，AM和CZ可显著降低CKD大鼠的血清肌酐（Scr）和血尿素氮（BUN）水平，并减轻肾脏病理损伤。通过在正离子模式和负离子模式下比较正常组和模型组的内源性成分，分别筛选出365种和155种不同的代谢物。在正离子模式和负离子模式下，模型组与AM和CZ组之间分别鉴定出117种和73种表达有显著差异的代谢物。AM和CZ影响的关键途径包括烟酸和烟酰胺代谢以及甘氨酸、丝氨酸和苏氨酸代谢。此外，观察到AM和CZ治疗后CKD大鼠代谢物有显著变化，包括L-苏氨酸、D-泛酸和烟酰胺。此外，我们发现AM和CZ可显著减轻CKD大鼠的肾纤维化和炎症，这可能与SIRT1/JNK信号通路的调节有关。总之，AM和CZ可显著减轻CKD大鼠的肾纤维化和炎症，这可能与SIRT1/JNK信号通路的调节有关。此外，L-苏氨酸、D-泛酸和烟酰胺可能是CKD进展和治疗的潜在生物标志物。
