Feng Yanhuan, Li Lingzhi, Guo Fan, Li Yanping, Liang Yan, Bai Lin, Ma Liang, Fu Ping
Kidney Research Laboratory, Division of Nephrology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University Chengdu 610041 China
Laboratory of Clinical Pharmacy and Adverse Drug Reaction, Department of Pharmacy, West China Hospital of Sichuan University Chengdu 610041 China.
RSC Adv. 2018 Dec 3;8(70):40232-40242. doi: 10.1039/c8ra08049f. eCollection 2018 Nov 28.
Renal interstitial fibrosis is the common pathway underlying the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) and the corresponding therapies are limited. Quantitative and qualitative alterations in gut microbiota are noted in patients with CKD and ESRD. In our previous study, SKLB023 exhibited antifibrotic effects by interfering TGF-β1/Smad3 signaling in obstructive nephropathy. However, it remained unclear that oral administration of SKLB023 drives the alteration of gut microbiota to attenuate renal fibrosis. In the study, the marked inflammation and interstitial fibrosis were found in the kidney tissues of unilateral ureteral obstruction (UUO) mice. While treatment with SKLB023 significantly alleviated renal interstitial fibrosis and reduced serum proinflammatory cytokines TNF-α, IL-6 levels. Importantly, SKLB023 derived the modulation of gut microbiota with the increasing similarity between the composition of gut microbiota in the control and UUO. The number of and was significantly decreased following UUO surgery and recovered by SKLB023, which positively correlated with pro-inflammatory cytokine expression. These results indicated the potential relationship between the antifibrotic benefits of SKLB023 and gut microbiota alteration, which provided new insights into drug therapy gut microbiota modulation in obstructive nephropathy.
肾间质纤维化是慢性肾脏病（CKD）进展至终末期肾病（ESRD）的共同途径，且相应的治疗方法有限。CKD和ESRD患者的肠道微生物群存在数量和质量上的改变。在我们之前的研究中，SKLB023通过干扰梗阻性肾病中的TGF-β1/Smad3信号传导发挥抗纤维化作用。然而，口服SKLB023是否通过驱动肠道微生物群的改变来减轻肾纤维化仍不清楚。在该研究中，单侧输尿管梗阻（UUO）小鼠的肾组织中发现了明显的炎症和间质纤维化。而SKLB023治疗显著减轻了肾间质纤维化，并降低了血清促炎细胞因子TNF-α、IL-6水平。重要的是，SKLB023促使肠道微生物群发生调节，使对照组和UUO组肠道微生物群组成之间的相似性增加。UUO手术后， 和 的数量显著减少，而SKLB023使其恢复，这与促炎细胞因子表达呈正相关。这些结果表明SKLB023的抗纤维化益处与肠道微生物群改变之间的潜在关系，为梗阻性肾病中药物治疗和肠道微生物群调节提供了新的见解。
