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肾脏病与透析肾移植杂志 ›› 2025, Vol. 34 ›› Issue (6): 524-531.DOI: 10.3969/j.issn.1006⁃298X.2025.06.004

• 论著 • 上一篇    下一篇

能量限制通过调控肠道金氏拟杆菌改善急性肾损伤

  

  • 出版日期:2025-12-28 发布日期:2025-12-29

Caloric restriction improves acute kidney injury by modulating gut microbiota Parabacteroides goldsteinii

  • Online:2025-12-28 Published:2025-12-29

摘要: 目的:探讨能量限制(CR)对缺血再灌注诱导的小鼠急性肾损伤(AKI)作用及机制。方法:将 C57BL/6J 雄性小鼠随机分为:假手术组(Sham)、肾缺血再灌注损伤(IRI)组、Sham+CR 组、IRI+CR 组、IRI + 抗生素清扫(ABX)组、IRI+ABX+CR 组、IRI + 金氏拟杆菌(PG)组、IRI + 灭活金氏拟杆菌(KPG)组,每组 6 只。IRI 24h 后,收集小鼠肾脏组织及血清标本。采用 HE 染色观察各组肾脏组织的病理变化,使用试剂盒检测小鼠血尿素氮(BUN)、血清肌酐(SCr)的变化,采用 qRT-PCR 和 Western Blot 检测肾脏损伤相关基因的表达,16S rRNA 检测小鼠粪便中的肠道菌群的变化。结果:与 Sham 组相比,IRI 组小鼠 BUN 和 SCr 升高(P<0.05),肾脏中肾损伤分子 1(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平增高(P<0.05),肾小管损伤严重(P<0.05)。与 IRI 组相比,IRI+CR 组小鼠 BUN 和 SCr 降低(P<0.05),肾脏中 KIM-1 和 NGAL 的表达降低(P<0.05),肾损伤程度减轻(P<0.05)。与 IRI+ABX 组相比,IRI+ABX+CR 组小鼠结肠组织的闭锁小带蛋白(ZO-1)和闭合蛋白(Occludin)的表达显著增加(P<0.05)。16S rRNA 结果显示 CR 处理的小鼠粪便中 PG 的丰度增加(P<0.05),肠道定植 PG 有效抑制 IR 引起的肾脏病理改变和肠道屏障功能的破坏。结论:CR 对 IRI 肾脏有保护作用,其机制可能与上调 PG 及增加肠道紧密连接蛋白表达有关。

关键词: font-family:Inter, -apple-system, BlinkMacSystemFont, ", font-size:16px, background-color:#FFFFFF, ">急性肾损伤、能量限制、肠道菌群、金氏拟杆菌、肠道屏障

Abstract: Objective: To investigate the effects of caloric restriction (CR) on ischemia-reperfusion-induced acute kidney injury (AKI) in mice and to explore the underlying mechanisms. Methodology: Male C57BL/6J mice were randomly assigned to the following groups: sham surgery (Sham), ischemia-reperfusion injury (IRI), Sham+CR, IRI+CR, IRI+antibiotic clearance (IRI+ABX), IRI+ABX+CR, IRI+Parabacteroides goldsteinii (PG), and IRI+heat-killed PG (KPG). Kidney pathology was assessed by hematoxylin and eosin (HE) staining. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were measured using assay kits. The expression of kidney injury markers was analyzed by quantitative real-time PCR and Western blotting. Gut microbiota composition was assessed by 16S rRNA sequencing of fecal samples. Results: Compared with the Sham group, IRI mice showed elevated BUN and SCr levels (P<0.05), increased renal expression of KIM-1 and NGAL (P<0.05), and severe tubular injury (P<0.05). CR significantly attenuated these effects: in IRI+CR mice, BUN and SCr levels were reduced (P<0.05), KIM-1 and NGAL expression decreased (P<0.05), and renal pathology improved (P<0.05). Moreover, CR upregulated the expression of colonic tight junction proteins ZO-1 and Occludin (P<0.05) and increased the abundance of PG (P<0.05). Colonization with PG, but not heat-killed bacteria, alleviated IRI-induced kidney injury and preserved intestinal barrier function. Conclusion: CR protects against renal IRI, at least in part, by enhancing intestinal barrier integrity through the enrichment of PG and upregulation of tight junction proteins.

Key words: font-family:Inter, -apple-system, BlinkMacSystemFont, ", font-size:16px, background-color:#FFFFFF, ">acute kidney injury, caloric restriction, gut microbiota, Parabacteroides goldsteinii, intestinal barrier