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

  
@article{APS10187,
	author = {Chen-chen Lu and Ze-bo Hu and Ru Wang and Ze-hui Hong and Jian Lu and Pei-pei Chen and Jia-xiu Zhang and Xue-qi Li and Ben-yin Yuan and Si-jia Huang and Xiong-zhong Ruan and Bi-cheng Liu and Kun-ling Ma},
	title = {Gut microbiota dysbiosis-induced activation of the intrarenal renin–angiotensin system is involved in kidney injuries in rat diabetic nephropathy},
	journal = {Acta Pharmacologica Sinica},
	volume = {41},
	number = {8},
	year = {2020},
	keywords = {},
	abstract = {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},
	url = {http://www.chinaphar.com/article/view/10187}
}