Relaxin-3 Ameliorates Diabetic Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress

Abstract

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 ( $n=20$ ) and diabetes ( $n=60$ ). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 μg/kg/d), and high-dose relaxin-3 group (2 μg/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)-1α, and tumor necrosis factor (TNF)-α 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 ( $P<0.01$ ). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group ( $P<0.05$ ). (3) IL-17, IL-1α, and TNF-α levels in the DM rats at 4 weeks were higher than in the controls ( $P<0.05$ ). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF-α levels compared with the DM group at four and eight weeks ( $P<0.05$ ). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls ( $P<0.01$ ), 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.