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APS Southeast University Affiliated Zhongda Hospital: the activation of renin-angiotension system caused by intestinal flora disorder is related to the renal injury of diabetic nephropathy in rats

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On March 17, 2020, Ma Kunling, associate professor of Southeast University Affiliated Hospital of CUHK, published in the academic journal Acta pharmacologica Sinica, entitled "git microbiology induced activation of the internal renin – angiotensin system is involved in kidney inventions in rapid development" In this study, SD rats were injected with streptozotocin to induce diabetic animal model. In addition, the relationship between intestinal flora and its metabolite acetate and early diabetic nephropathy was explored by using broad-spectrum antibiotics to construct animal model of eliminating flora. It was found that the intestinal flora and its acetate metabolite of early diabetic nephropathy had significant changes, The relationship between these changes and the renin-angiotension system in the kidney was further explored. In the future, we need to further explore the causal relationship and mechanism between intestinal flora and activation of renin-angiotension system in early diabetic nephropathy, so as to develop new prevention strategies for early diabetic nephropathy.
Article summary
Previous studies have found that intestinal flora and its metabolites are closely related to diabetes mellitus (DM). In this study, the authors explored the relationship between intestinal flora and renal damage in early diabetic nephropathy (DN) and its underlying mechanism. Streptozotocin was injected into the peritoneum of male SD rats to induce diabetes. Diabetic nephropathy rats were treated with broad-spectrum antibiotics for 8 weeks. After the rats were killed, blood, urine, feces and kidney tissues were collected for analysis. The results showed that compared with the control group, diabetic rats had intestinal flora disorder, plasma acetate level increased, proteinuria increased, glomerular basement membrane thickened and podocyte foot process disappeared. In addition, the protein levels of Ang II, ACE and Ang II type 1 receptor in the kidney of diabetic rats increased significantly. The treatment with broad-spectrum antibiotics can not only eliminate most intestinal flora, but also significantly reduce the level of plasma acetate, inhibit the activation of renal renin-angiotension system (RAS) and reduce renal damage. Finally, we found that there was a positive correlation between the level of acetate in plasma and the expression of Ang II protein in kidney (r = 0.969, P & lt; 0.001). In conclusion, the excess acetic acid produced by intestinal flora disturbance may be involved in the renal injury of early diabetic nephropathy by activating intrarenal RAS.
Important pictures in the article
Figure 1 three experimental parameters. a. Blood glucose level, B insulin level.
Fig. 2 Changes of intestinal flora in three groups. a. Lefse analysis, B. relative abundance of blautia in three groups of intestinal flora, C. relative abundance of Roseburia in three groups of intestinal flora, D. relative abundance of paraprevotella in three groups of intestinal flora, e. relative abundance of Bacteroides in three groups of intestinal flora.
Fig. 3 antibiotic treatment can significantly reduce the level of acetate in plasma.
Fig. 4 Effect of intestinal flora on renal index of early diabetic nephropathy. a. The ratio of kidney weight to body weight, B. 24-hour urine protein, C. blood urea nitrogen level, D. blood creatinine.
Fig. 5 Effect of intestinal flora on renal injury in early diabetic nephropathy. a. PAS staining, B. glomerular expansion score, C. podocyte changes, D. WGA staining, e. immunofluorescence staining, F. WT-1 immunofluorescence staining, G, nephrin immunofluorescence staining.
Figure 6 early diabetic nephropathy activates renin-angiotension system.
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