The effect of intravenous injection of c-kit + stem cells on autophagy-related genes in heart tissue of type 2 diabetic induced by a high-fat diet/low-dose streptozotocin in male rats

Abstract

In recent years, the prevalence of diabetes in the world has increased, therefore cardiac dysfunction caused by this disease is emerging as a serious and urgent challenge. Autophagy, which is a physiological catabolic process, is disturbed in diabetes. Considering the importance of finding a method to treat heart dysfunction following diabetes and the lack of clarity about the mechanism of action of c-kit+ stem cells in this regard, we decided to investigate the effect of the injection of c-kit+ stem cells extracted from the bone marrow on the expression level for the first time. To investigate the genes affecting autophagy in heart tissue of type 2 diabetic male rats induced by high-fat diet and low-dose streptozotocin.

Methods In this study, 58 male rats were examined according to the following groups (12 rats in each group): 10 animals were randomly selected to extract c-kit⁺ and c-kitˉ stem cells, and the rest were randomly selected. They were divided into 4 groups: control (C), diabetic (D), diabetic + c-kit+ cells (D+ c-kit+) and diabetic + c-kit- (D+ c-kit-). In order to induce diabetes, they were subjected to a high-fat diet followed by an intraperitoneal injection of streptozotocin (35 mg/kg). c-kit+ and c-kit- cells were extracted from the bone marrow of 10 selected animals, then c-kit+ cells were separated using MACS method. The extracted cells were injected intravenously. 60 days later, the animals were anesthetized with ketamine and xylazine injections, and their heart tissue was removed to examine the pathology and expression levels of genes related to autophagy.

Result The findings of this study showed a decrease in the expression of BECLIN, LC3, and p62 genes in the heart tissue of the diabetic group compared to the control group. Injection of c-kit + cells improved the expression of the above genes.