Gut microbiota dysbiosis-induced activation of the intrarenal renin-angiotensin system is involved in kidney injuries in rat diabetic nephropathy
Gut microbiota dysbiosis-induced activation of the intrarenal renin-angiotensin system is involved in kidney injuries in rat diabetic nephropathy
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DOI：
10.1038/s41401-019-0326-5
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发表时间：
2020-03-17
影响因子：
8.2
通讯作者：
Ma，Kun-ling
中科院分区：
文献类型：
--
作者：
Lu，Chen-chen;Hu，Ze-bo;Ma，Kun-ling
一些研究表明，肠道微生物群沿着其代谢产物与糖尿病（DM）密切相关。本研究旨在探讨肠道菌群与早期糖尿病肾病（DN）肾损害的关系及其机制。雄性SD大鼠腹腔注射链脲佐菌素诱导DM。DM大鼠口服复方广谱抗生素8周。处死大鼠后，采集其血液、尿液、粪便和肾组织进行分析。我们发现，与对照组大鼠相比，DM大鼠肠道菌群异常，血浆醋酸水平升高，蛋白尿增加，肾小球基底膜增厚，肾脏足细胞足突消失。此外，糖尿病大鼠肾脏中血管紧张素II、血管紧张素转换酶和血管紧张素II 1型受体的蛋白水平显著升高。DM大鼠给予广谱抗生素不仅能完全杀死大多数肠道菌群，而且能显著降低血浆醋酸盐水平，抑制肾内RAS激活，减轻肾脏损害。血浆醋酸水平与肾内血管紧张素II蛋白表达呈正相关（r= 0.969，P < 0.001）。总之，肠道菌群失调产生的过量乙酸可能通过激活肾内RAS参与早期DN的肾损伤。
Some studies have shown that gut microbiota along with its metabolites is closely associated with diabetic mellitus (DM). In this study we explored the relationship between gut microbiota and kidney injuries of early diabetic nephropathy (DN) and its underlying mechanisms. Male SD rats were intraperitoneally injected with streptozotocin to induce DM. DM rats were orally administered compound broad-spectrum antibiotics for 8 weeks. After the rats were sacrificed, their blood, urine, feces, and renal tissues were harvested for analyses. We found that compared with the control rats, DM rats had abnormal intestinal microflora, increased plasma acetate levels, increased proteinuria, thickened glomerular basement membrane, and podocyte foot process effacement in the kidneys. Furthermore, the protein levels of angiotensin II, angiotensin-converting enzyme, and angiotensin II type 1 receptor in the kidneys of DM rats were significantly increased. Administration of broad-spectrum antibiotics in DM rats not only completely killed most intestinal microflora, but also significantly lowered the plasma acetate levels, inhibited intrarenal RAS activation, and attenuated kidney damage. Finally, we showed that plasma acetate levels were positively correlated with intrarenal angiotensin II protein expression (r= 0.969,P< 0.001). In conclusion, excessive acetate produced by disturbed gut microbiota might be involved in the kidney injuries of early DN through activating intrarenal RAS.