Modulatory Effects of Estradiol-Treated Mesenchymal Stem Cells’ Conditioned Medium on Impaired Cardiomyocytes in Nicotinamide/STZ-Induced Diabetic Male Rats: Study of PI۳K/Akt-Atrogin-۱ Signaling Axis

Diabetes mellitus is a metabolic disorder caused by insulin resistance or lack of insulin secretion. This disease is associated with cardiovascular disorders caused by oxidative stress, inflammation, and apoptosis. Previously, the therapeutic effects of stem cells have been shown in diabetes. In the present study, the effects of substances secreted from mesenchymal stem cells extracted from bone marrow with or without treatment with estradiol were evaluated on some characteristics of the cardiovascular system in male diabetic rats. In this study, ۲۲ male Wistar rats weighing ۱۹۰±۲۰ g were used. Two rats were used to extract the mesenchymal stem cells (MSCs) from bone marrow. Stem cells were exposed to ۰ or ۰.۱ mM Estradiol, and then, the conditioned media (CM and ECM) of the cells were harvested. Diabetes was induced by intraperitoneal injection of nicotinamide (۱۱۰ mg/kg) and then streptozotocin (۶۵ mg/kg). Diabetic animals were divided into three subgroups intraperitoneally receiving saline, CM, or ECM (۱۰۰ µl/rat) three times on days ۷, ۲۱, and ۳۵ after the beginning of the study. On the fiftieth day, a part of the cardiac apex was transferred to -۷۰ °C to evaluate the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and the expression of PI۳K, Akt, and Atrogin-۱ genes by the qRT-PCR method. The rest of the cardiac tissue was placed in formalin for histopathologic study. Advanced glycation end products (AGEs) were measured in serum. Diabetes significantly (p < ۰.۰۵) caused to decrease of TAC and to increase of MDA, PI۳K, Akt, and Atrogin-۱ mRNA expression in the heart, and the serum AGEs levels compared to control rats, and led to cardiac tissue damage. Administration of CM or ECM significantly (p < ۰.۰۵) modulated all indices except Akt expression levels. In conclusion, conditioned media of bone marrow mesenchymal stem cells, especially ECM, improved some cardiovascular disorders in diabetic rats.

کلیدواژه ها:

Diabetes ، Stem Cell ، Estradiol ، Conditional medium ، PI۳K/Akt