Gut microbiota dysbiosis-induced activation of the intrarenal renin-angiotensin system is involved in kidney injuries in rat diabetic nephropathy

• 作者: Ben-yin Yuan Bi-cheng Liu Chen-chen Lu Jia-xiu Zhang Jian Lu Kun-ling Ma Pei-pei Chen Ru Wang Si-jia Huang Xiong-zhong Ruan Xue-qi Li Ze-bo Hu Ze-hui Hong
• 来源期刊: 中国药理学报（英文版）
• 关键词: diabetic nephropathy gut microbiota plasma acetate renin-angiotensin system broad-spectrum antibiotics
• 年，卷（期）: 2020,（8）
• 页码范围: 1111-1118
• 页数: 8页
• 语种: 英文

摘要

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,udne,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.