Effects of Eight Weeks of Aerobic Training on Expression Levels of the HMGB1-RAGE/TLR4-NF-kB Proinflammatory Pathway in Cardiac Tissue of Male Rats with Hyperglycemia

Inflammation plays a critical role in the pathogenesis of diabetic cardiomyopathy. The expression of HMGB1, a proinflammatory cytokine, and its downstream signaling pathway is upregulated in diabetes. The aim of this study was to investigate the effect of 8 weeks aerobic training on the expression levels of the HMGB1-RAGE/TLR4-NF-kB pathway in cardiac tissue of male rats with hyperglycemia. Thirty-six male Wistar rats (mean weight, 231±25g) were randomly divided into three groups (n=12 each): Healthy control, control hyperglycemia and trained hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of strept ozotocin and nicotinamide. Forty-eight hours after completion of the training program (eight weeks aerobic training), cardiac tissue was removed under sterile conditions. Gene expression of HMGB1, RAGE, TLR4 and NF-kB were investigated, using Real-time PCR. For data analysis, one-way ANOVA and post-hoc Tukey’s test were used, with P<0.05 considered statistically significant. Gene expression levels of HMGB1, RAGE, TLR4 and NF-kB were significantly (P=0.001) increased in the cardiac tissue of the hyperglycemic control group, compared with healthy controls. Eight weeks of aerobic training decreased the expression levels of the studied genes (P=0.001). It seems that aerobic training can prevent the negative effects of hyperglycemia via by attenuating gene expression levels of HMGB1, RAGE, TLR4 and NF-kB in the cardiac tissue of rats with hyperglycemia, and could hence be an important mechanism for cardiac function and preventing diabetic cardiomyopathy.