State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, China.
Nutrients. 2021 Nov 1;13(11):3920. doi: 10.3390/nu13113920.
A high-salt diet (HSD) is one of the key risk factors for hypertension and kidney injury. In this study, a HSD C57BL/6J mice model was established with 4% NaCl, and then different concentrations of ZDY2013 were intragastrically administered for 2 weeks to alleviate HSD-induced renal injury. For the study, 16S rRNA gene sequencing, non-targeted metabonomics, real-time fluorescent quantitative PCR, and Masson's staining were used to investigate the mechanism of ZDY2013 in alleviating renal damage. Results showed that HSD caused intestinal inflammation and changed the intestinal permeability of mice, disrupted the balance of intestinal flora, and increased toxic metabolites (tetrahydrocorticosteron (THB), 3-methyhistidine (3-MH), creatinine, urea, and L-kynurenine), resulting in serious kidney damage. Interestingly, ZDY2013 contributed to reconstructing the intestinal flora of mice by increasing the level of and and decreasing that of and . Moreover, the reconstructed intestinal microbiota significantly changed the concentration of the metabolites of hosts through metabolic pathways, including TCA cycle, ABC transport, purine metabolism, and histidine metabolism. The content of uremic toxins such as L-kynurenine, creatinine, and urea in the serum of mice was found to be decreased by ZDY2013, which resulted in renal injury alleviation. Our data suggest that ZDY2013 can indeed improve chronic kidney injury by regulating intestinal flora, strengthening the intestinal barrier, limiting inflammatory response, and reducing uremic toxins.
高盐饮食（HSD）是高血压和肾损伤的关键风险因素之一。在本研究中，建立了 4%NaCl 的 HSD C57BL/6J 小鼠模型，然后用不同浓度的 ZDY2013 灌胃 2 周，以减轻 HSD 引起的肾损伤。本研究采用 16S rRNA 基因测序、非靶向代谢组学、实时荧光定量 PCR 和 Masson 染色，研究 ZDY2013 缓解肾损伤的作用机制。结果表明，HSD 导致肠道炎症和小鼠肠道通透性改变，破坏了肠道菌群的平衡，增加了有毒代谢物（四氢皮质甾酮（THB）、3-甲基组氨酸（3-MH）、肌酐、尿素和 L-犬尿氨酸），导致严重的肾损伤。有趣的是，ZDY2013 通过增加 和 的水平，降低 和 的水平，有助于重建小鼠肠道菌群。此外，重建的肠道微生物群通过包括 TCA 循环、ABC 转运、嘌呤代谢和组氨酸代谢在内的代谢途径显著改变宿主代谢物的浓度。ZDY2013 降低了血清中犬尿氨酸、肌酐和尿素等尿毒症毒素的含量，减轻了肾损伤。我们的数据表明，ZDY2013 确实可以通过调节肠道菌群、增强肠道屏障、限制炎症反应和减少尿毒症毒素来改善慢性肾损伤。
