Relaxin-3 Ameliorates Diabetic Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress.

BACKGROUND

This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS.

METHODS

Eighty male SD rats were randomly divided into two groups: controls ( = 20) and diabetes ( = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 g/kg/d), and high-dose relaxin-3 group (2 g/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1, and tumor necrosis factor (TNF)- were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis.

RESULTS

(1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls ( < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group ( < 0.05). (3) IL-17, IL-1, and TNF- levels in the DM rats at 4 weeks were higher than in the controls ( < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF- levels compared with the DM group at four and eight weeks ( < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls ( < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression.

CONCLUSIONS

Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats.