肠道菌群移植保护大鼠肾脏缺血再灌注损伤

Fecal microbiota transplantation protects against renal ischemia-reperfusion injury in rats

摘要

目的 本研究通过构建大鼠肾脏缺血再灌注（IRI）模型系统评价了预防性粪菌移植（FMT）的肾脏保护作用。方法 将雄性SD大鼠随机分组，其中IRI+FMT组在造模前连续7 d经灌胃接受豚鼠来源的粪便微生物肠溶胶囊干预。结果 研究结果显示，与IRI+NS对照组相比，IRI+FMT组大鼠的肾功能指标显著改善，血清肌酐和尿素氮水平明显降低（P＜0.001）。苏木精-伊红（HE）染色表明，FMT有效减轻了肾组织病理损伤，包括肾小管上皮空泡化、间质充血及水肿。在炎症反应方面，FMT干预显著降低了血清中IL-1α、TNF-α、IL-6及MCP-1等促炎因子的蛋白水平，并同时抑制了肾脏局部炎症介质mRNA的表达。TUNEL染色进一步证实FMT可显著减少肾小管细胞凋亡。通过16S rRNA测序分析发现，FMT处理重塑了大鼠肠道菌群结构，Chao1指数和香农指数显著升高（P＜0.01），β多样性分析显示组间微生物群落明显分离，其中毛螺菌科（Lachnospiraceae）在科水平的相对丰度显著增加。结论 预防性FMT可通过调节肠道菌群组成，减轻IRI后的肾功能障碍、炎症反应及细胞凋亡，从而发挥肾脏保护效应。

Abstract

Objective This study systematically evaluated the renal protective effects of preventive fecal microbiota transplantation（FMT）by establishing a rat model of renal ischemia-reperfusion injury（IRI）. Methods Male Sprague-Dawley（SD）rats were randomly assigned into groups. The IRI+FMT group received guinea pig-derived fecal microbiota enteric-coated capsules via gavage for 7 consecutive days prior to model establishment. Results Prophylactic FMT significantly ameliorated renal impairment in IRI rats. Compared with the IRI+NS group，the IRI+FMT group showed markedly improved renal function，with reduced serum creatinine and blood urea nitrogen levels（P＜0.001）. HE staining revealed that FMT attenuated pathological damage，including tubular vacuolization，interstitial congestion and edema. FMT also significantly decreased serum levels of proinflammatory cytokines such as IL-1α，TNF-α，IL-6，and MCP-1，and suppressed the mRNA expression of inflammatory mediators in renal tissue. TUNEL staining confirmed that FMT reduced tubular cell apoptosis. 16S rRNA sequencing indicated that FMT reshaped the gut microbiota structure，increasing Chao1 and Shannon indices（P＜0.01）. Beta diversity analysis showed clear separation between microbial communities，with a significant increase in the relative abundance of Lachnospiraceae at the family level. Conclusion Prophylactic FMT may exert renoprotective effects by modulating the gut microbiota，thereby attenuating renal dysfunction，inflammatory response，and cellular apoptosis following IRI.

关键词

粪便微生物群移植 / 急性肾损伤 / 缺血再灌注损伤 / 毛螺菌科

Key words

fecal microbiota transplantation / acute kidney injury / ischemia-reperfusion injury / Lachnospiraceae

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基金资助

湖北省自然科学基金项目(2023AFB498)

武汉市自然科学基金探索计划（晨光计划）(2024040801020363)