Effect of apelin-13 on myocardium apoptosis in diabetic rats

Abstract

Objective To investigate the effect of exogenous apelin-13 on oxidative stress, myocardial inflammatory cytokines and apoptosis in diabetic model rats. Methods A total of 40 male Wistar rats were randomly divided into 2 groups: normal control group (NC, n=8) and experimental group (EX, n=32). Diabetes was induced by feeding with high-sugary and high-fat diet for 8 weeks and a single intraperitoneal injection of streptozotocin (STZ) (30 mg/kg). The well-established 28 diabetic model rats were then randomly divided into 2 subgroups: model group (DM, n=14) and apelin-13 administration group (AP, n=14). The rats in AP group were given intraperitoneal administration of apelin-13 at a single dose of 0.1 μmol·kg-1·d-1 for 10 weeks, while NC group and DM group were given 0.9% NaCl in the same way. All rats were sacrificed at the end of the week 10. Blood hydrogen peroxide (H2O2), nitric oxide (NO) and malonaldehyde (MDA) were measured by colorimetry, and superoxide dismutase (SOD) was measured by enzyme-linked immunosorbent assay (ELISA). The expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rat myocardium were detected by immunohistochemistry.Masson staining was used to observe the myocardial fibrosis in rats of different groups. Cardiomyocyte apoptosis was determined by TUNEL. Results (1) Compared with NC groups, DM group showed that MDA, H2O2and NO were significantly increased, while SOD was significantly decreased (F=22.400, 6.230, 4.267 and 8.901, all P<0.0167). There was a statistically significant difference in the levels of MDA, H2O2,SOD between DM group and AP group. (2) The expression of TNF-α and IL-6 was significantly higher in DM group than in NC group (0.0599±0.0208 vs. 0.0076±0.0031, F=35.139; 0.0503±0.0243 vs. 0.0071±0.0024, F=15.946, both P<0.0167). After 10 weeks of apelin-13 administration, the levels of inflammatory cytokines were significantly decreased in AP group than in DM group. (3) The myocardial apoptosis and fibrosis were significantly increased in DM group than in NC group 〔0.0293±0.0061 vs. 0.0030±0.0013 and 0.0708±0.0420 vs. 0.0013±0.0003, F=84.930 and 19.420, both P<0.0167〕. The myocardial apoptosis and fibrosis were significantly decreased in AP group than in DM group (both P<0.0167). Conclusions To some extent, apelin-13 reduces the levels of oxidative stress and myocardial inflammation reaction in type 2 diabetes. Moreover, it may play a vital role in the improvement of myocardial apoptosis and fibrosis. Key words: Diabetes mellitus; Apoptosis; Myocytes, cardiac; Adipokines