Abstract: TH-PO078

Microecological Imbalance of Intestinal Microflora Activates Renal Renin-Angiotensin System to Contribute to the Progression of Early Diabetic Nephropathy

Session Information

Category: Glomerular

  • 1002 Glomerular: Basic/Experimental Pathology

Authors

  • Lu, Chenchen, Institute of Nephrology, Zhong Da Hospital, Nan Jing City, China
  • Ma, Kun ling, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Zhang, Yang, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Wang, Gui hua, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Hu, Zebo, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Chen, Peipei, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
  • Lu, Jian, Zhongda Hospital, Southeast University Medical School, Nanjing City, JIANGSU , China
Background

It is well-known that activated renal rennin-angiotensin (RAS) plays a key role in the development of early diabetic nephropathy (DN). However, the initiating factors and potential mechanisms led to RAS activation have not been fully elucidated. This study aimed to investigate the underlying mechanisms of how abnormal intestinal microenvironment activates RAS to contribute to early renal injuries of DN.

Methods

Streptozotocin-induced diabetic rat model was randomly divided into three groups: Control group, diabetic group (DM), and diabetic+antibiotics (DM+AB) group. The rats of DM+AB group were fed for 8 weeks with regular chow and antibiotic mixed liquor (ampicillin 1g/L + vancomycin 0.5g/L + neomycin 1g/L + amphotericin B 0.1g/L). Gene sequencing of intestinal microflora was carried out using 16S-rDNA pyrosequencing technique. The morphological changes to the renal pathology and ultra-microstructures were checked by pathological staining and electron microscopy. The plasma RAS components were determined by radioimmunoassay. The protein expressions of RAS components in the kidneys were determined by immunohistochemical staining and Western blot.

Results

Compared with control group, DM group showed with abnormal intestinal microflora, which significantly increase the production of acetate in the plasma. There were increased ACR, thickened glomerular basement membrane, podocyte foot process effacement in kidneys of DM group compared with the controls. The plasma levels of angiotensin II and the protein levels of angiotensinogen, angiotensin II, renin, angiotensin-converting enzyme, and angiotensin II type 1 receptor in the kidneys of DM group were significantly increased compared to the controls, which were positively associated with kidney injuries of DM group. However, in DM+AB group, after intestinal microflora were completely killed by antibiotics, kidney damage and RAS activation were weakened accordingly compared with the DM group.

Conclusion

These findings suggest that microecological imbalance of intestinal microflora might be a potential mechanism for the progression of early DN, which leads to kidney injuries via the RAS activation.