Shenyan Kangfu tablet alleviates diabetic kidney disease through attenuating inflammation and modulating the gut microbiota
Shenyan Kangfu tablet alleviates diabetic kidney disease through attenuating inflammation and modulating the gut microbiota
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DOI：
10.1007/s11418-020-01452-3
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发表时间：
2020-09-30
影响因子：
3.3
通讯作者：
Wang, Tao
中科院分区：
文献类型：
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作者：
Chen, Qian;Ren, Dongwen;Wang, Tao
炎症在糖尿病肾病（DKD）的发病机制中起主导作用。肾炎康复片（SYKFT）是治疗慢性肾脏病的中药处方。然而，具体机制尚不清楚。根据前期的临床试验，我们探讨了SYKFT在db/db模型中对DKD的影响及其可能的机制。结果，SYKFT降低了受刺激的血糖和HbA1c水平，减轻了db/db小鼠的肾功能障碍、肾小球和小管损伤以及肾脏炎症（tnf - α和IL-1 β）。初步机制研究表明，SYKFT改善肾损伤主要与体内和体外抑制nf - κ B有关。本研究进一步观察到SYKFT增加了厚壁菌门的相对丰度，降低了拟杆菌门的相对丰度，表明代表性微生物群的相对丰度与肾功能参数直接相关。SYKFT可有效降低拟杆菌的相对丰度，且NF-kappa B、tnf - α和IL-1 β的相对丰度与蛋白表达呈正相关，表明SYKFT的抗炎活性与调节肠道菌群有关。因此，我们首次证明SYKFT通过调节肾脏炎症信号级联和肠道微生物群来减轻DKD，并指出特定肠道微生物群在DKD发生中的作用。
Inflammation plays a predominant role in the pathogenesis of diabetic kidney disease (DKD). The Shenyan Kangfu tablet (SYKFT) is a prescription of traditional Chinese medicine for treating chronic kidney disease. However, the concrete mechanism is still unclear. According to previous clinical trial, we explored the effects and potential mechanism on DKD in db/db model supplemented with SYKFT. As a result, SYKFT reduced stimulated blood glucose and HbA1c levels, alleviated renal dysfunction, glomerular and tubular damage, and renal inflammation (TNF-alpha and IL-1 beta) in db/db mice. The primary mechanistic study illustrated that SYKFT improved renal injury mainly associated with inhibition of NF-kappa B in vivo and in vitro. This study further observed that SYKFT increased relative abundance of Firmicutes and decreased Bacteroidetes, showing direct correlation between representative microbiota relative abundance and renal function parameters. SYKFT effectively decreased the relative abundance of Bacteroides, and positive correlation between the relative abundance and protein expression of NF-kappa B, TNF-alpha and IL-1 beta predicted that anti-inflammatory activity of SYKFT was associated with modulating the gut microbiota. Therefore, we first demonstrated SYKFT alleviated DKD through regulating renal inflammatory signaling cascades and intestinal microbiota and also pointed out the role of specific gut microbiota in the development of DKD.