METFORMIN EFFECT ON THE TUBULOINTERSTITIAL FIBROSIS DEVELOPMENT IN RATS

THE AIM - to study the effect of metformin on the tubulointerstitial fibrosis development and microRNA 21 expression in urine on the model of unilateral ureteral obstruction (UUO) in rats. MATERIAL AND METHODS. Male Wistar rats weighing 230-250 g were used for modeling tubulointerstitial fibrosis following UUO. The first group (control; n = 5) rats received a standard diet, the animals of the second group (n = 5) immediately after surgery received standard diet and metformin 10 mg per day. Both groups of rats were observed for 14 days after the UUO modeling. One day before the experiment termination, in rats which were placed in a metabolic chamber urine was collected during 24 hours for subsequent miRNA 21 expression determination. After removal the animal from the experiment received samples of urine from the renal pelvis of the kidney with UUO to determine miRNA 21 expression, as well as samples of kidney tissue for subsequent histological examination. Severity of morphological changes were evaluated by quantitative morphometry to determine the relative volume of tubulointerstitium (RVTin) and relative volume of the tubular epithelium (RVTe). RESULTS. In the control group, the experimental UUO led to a logical, a statistically significant increase in RVTin compared with the contralateral kidney. Similar data were obtained by the group of animals treated with metformin. Metformin had no significant effect on the severity of RVTin neither contralateral (intact) kidney, nor kidney with UUO. UUO in animals treated with metformin resulted in a significant decrease in the value RVTe. There were no significant differences in the levels of RVTe in the intact kidneys or kidney with OOM in animals receiving and not receiving metformin. CONCLUSION. The obtained results have not confirmed nephroprotective effect of metformin on the tubulointerstitial fibrosis development in rats with UUO. However for the final resolve of this problem requires additional clinical and experimental studies.

metformin, tubulointerstitial fibrosis, unilateral ureteral obstruction, miRNA-21

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