Experimental therapy of chronic kidney ischemia using drug basic fibroblast growth factor

Abstract

Abstract. The aim of the work was to experimentally study the effect of the created injectable drug basic fibroblast growth factor (bFGF) with the controlled release on morphological changes and indicators of renospecific enzymes in the ischemic kidney (experiment on rabbits). Methods. Studies on the release dynamics of the created bFGF drug were performed in vitro and the study of the induction of bFGF angiogenesis in the model of the chick chorioallantoic membrane of the chicken was performed. The experimental model was performed in 25 rabbits: in 10 rabbits we studied the effect of 1-8 months of "pure ischemia" of the kidney without injection of the drug (control); in 12 rabbits 1 month after the creation of the model of ischemia in the renal parenchyma was injected the prolonged-acting drug bFGF, deposited on our polymeric carrier at a dose of 5 μg (experiment). The reference group consisted of 3 intact rabbits. Histological examinations of renal tissue and morphometric examinations with the determination of vascular coefficient (VC) and interstitial coefficient (IC) were performed. Enzymological indicators of enzyme activity in the homogenate of the renal parenchyma were determined by biochemical methods; statistical analysis was performed. Results. Using chick chorioallantoic membrane as a model it was preliminarily demonstrated that developed injectable prolonged-acting drug bFGF deposited on a polymeric carrier based on cross-linked modified heparin, effectively enhances neoangiogenesis. The results of morphological and morphometric studies with the determination of vascular and interstitial coefficients showed, that the injection of the prolonged-acting drug bFGF in all cases was accompanied by an increased blood supply in the kidneys and neoangiogenesis, which reduced the effects of ischemia. Injection of bFGF at a dose of 5 μg in the model of chronic segmental renal ischemia for 3-4 months completely prevented the development of initial sclerotic and atrophic changes, that developed in the kidney during this period under the influence of chronic ischemia without bFGF. Injection of prolonged-acting bFGF at a dose of 5 μg in the model of chronic segmental renal ischemia for 5-8 months prevented expressed sclerotic and atrophic changes, that developed under the influence of chronic ischemia during this period without the use of bFGF. As a result of biochemical studies, the activation and normalization of indicators of renospecific tubular enzymes in the ischemic kidney under the action of the created experimental drug bFGF were determined. Conclusions. Therapy of ischemic changes in the kidney with the developed injectable long-acting drug bFGF at a dose of 5 µg in the experimental model of chronic ischemia protects the organ from hypoxic damage, has a positive effect on the structural and functional state and metabolism of the kidney, and prevents the development of nephrosclerosis.

Keywords

• chronic kidney ischemia, basic fibroblast growth factor, vascular coefficient, interstitial coefficient, enzymes.