Shen Xiaoyan, Dong Xianan, Han Yuli, Li Yan, Ding Shixin, Zhang Han, Sun Zhenghao, Yin Yanyan, Li Weiping, Li Weizu
Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University, Hefei 230032, Anhui, China.
Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University, Hefei 230032, Anhui, China; Anqing Medical and Pharmaceutical College, Anqing 246052, Anhui, China.
Int Immunopharmacol. 2020 Feb 27;82:106339. doi: 10.1016/j.intimp.2020.106339.
Aging is closely related to the progress of renal fibrosis, which eventually results in renal dysfunction. Ginsenoside Rg1 (Rg1) has been reported to have an extensive anti-aging effect. However, the role and mechanism of Rg1 in aging-related renal fibrosis remain unclear. The present study aimed to evaluate the protective effect and mechanism of Rg1 in renal fibrosis during kidney aging in a model of SAMP8 mice. Taking SAMR1 mice as the control group, SAMP8 mice were administered Apocynin (50 mg/kg), Tempol (50 mg/kg), or Rg1 (5, 10 mg/kg) intragastrically for 9 weeks as treatment groups. The results showed that the elevated levels of blood urea nitrogen, serum creatinine and senescence-associated β-galactosidase (β-Gal) were markedly decreased, the glomerular mesangial proliferation was significantly alleviated and the increased levels of collagen IV and TGF-β1 were significantly downregulated by Rg1 in SAMP8 mice. In addition, the generation of ROS and the expression of NADHP oxidase 4 (NOX4) in the renal cortex were significantly reduced by Rg1 treatment. The expression levels of NLRP3 inflammasome-related proteins and the inflammation-related cytokine IL-1β were also inhibited by Rg1 treatment in the SAMP8 mice. These results suggested that Rg1 could delay kidney aging and inhibit aging-related glomerular fibrosis by reducing NOX4-derived ROS generation and downregulating NLRP3 inflammasome expression.
衰老与肾纤维化的进展密切相关，最终导致肾功能障碍。据报道，人参皂苷Rg1（Rg1）具有广泛的抗衰老作用。然而，Rg1在衰老相关肾纤维化中的作用和机制仍不清楚。本研究旨在评估Rg1在SAMP8小鼠模型肾衰老过程中对肾纤维化的保护作用及机制。以SAMR1小鼠作为对照组，将SAMP8小鼠作为治疗组，分别灌胃给予阿朴吗啡（50mg/kg）、Tempol（50mg/kg）或Rg1（5、10mg/kg），持续9周。结果显示，Rg1可使SAMP8小鼠升高的血尿素氮、血清肌酐和衰老相关β半乳糖苷酶（β-Gal）水平显著降低，肾小球系膜增殖明显减轻，IV型胶原和TGF-β1升高水平显著下调。此外，Rg1处理可显著降低肾皮质中ROS的生成及NADHP氧化酶4（NOX4）的表达。Rg1处理还可抑制SAMP8小鼠中NLRP3炎性小体相关蛋白的表达水平及炎症相关细胞因子IL-1β。这些结果表明，Rg1可通过减少NOX4衍生的ROS生成和下调NLRP3炎性小体表达来延缓肾脏衰老并抑制衰老相关的肾小球纤维化。
