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H3 Relaxin Protects Against Myocardial Injury in Experimental Diabetic Cardiomyopathy by Inhibiting Myocardial Apoptosis, Fibrosis and Inflammation.
Zhang, Xiaohui; Pan, Liya; Yang, Kelaier; Fu, Yu; Liu, Yue; Chi, Jinyu; Zhang, Xin; Hong, Siting; Ma, Xiao; Yin, Xinhua.
Afiliação
  • Zhang X; The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Pan L; The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Yang K; The Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Fu Y; The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Liu Y; The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Chi J; The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Zhang X; The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Hong S; The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Ma X; The Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
  • Yin X; The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Cell Physiol Biochem ; 43(4): 1311-1324, 2017.
Article em En | MEDLINE | ID: mdl-28992627
ABSTRACT
BACKGROUND/

AIMS:

Apoptosis, fibrosis and NLRP3 inflammasome activation are involved in the development of diabetic cardiomyopathy (DCM). Human recombinant relaxin-3 (H3 relaxin) is a novel bioactive peptide that inhibits cardiac injury; however, whether H3 relaxin prevents cardiac injury in rats with DCM and the underlying mechanisms are unknown.

METHODS:

To investigate the effect of H3 relaxin on DCM, we performed a study using H3 relaxin treatment in male Sprague-Dawley (SD) rats with streptozotocin (STZ)-induced diabetes (DM). We measured apoptosis, fibrosis and NLRP3 inflammasome markers in the rat hearts four and eight weeks after the rats were injected with STZ (65 mg/kg) by western blot analysis. Subsequently, 2 or 6 weeks after the STZ treatment, the rats were treated with H3 relaxin [2 µg/kg/d (A group) or 0.2 µg/kg/d (B group)] for 2 weeks. Cardiac function was evaluated by echocardiography to determine the extent of myocardial injury in the DM rats. The protein levels of apoptosis, fibrosis and NLRP3 inflammasome markers were used to assess myocardial injury. In addition, we determined the plasma levels of IL-1ß and IL-18 using a Milliplex MAP Rat Cytokine/Chemokine Magnetic Bead Panel kit.

RESULTS:

The protein expression of cleaved caspase-8, caspase-9 and caspase-3 as well as fibrosis markers increased at 4 and 8 weeks in the STZ-induced diabetic hearts compared with the levels in the control group. Furthermore, the NLRP3 inflammasome was substantially activated in STZ-induced diabetic hearts, leading to increased IL-1ß and IL-18 levels. Compared with the DM group, the A group exhibited substantially better cardiac function. The protein levels of apoptosis markers were attenuated by H3 relaxin, indicating that H3 relaxin inhibited myocardial apoptosis in the hearts of diabetic rats. The protein expression of fibrosis markers was inhibited by H3 relaxin. Additionally, the protein expression and activation of the NLRP3 inflammasome were also effectively attenuated by H3 relaxin.

CONCLUSIONS:

This study is the first to demonstrate that H3 relaxin plays an anti-apoptotic, anti-fibrotic and anti-inflammatory role in DCM.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Relaxina / Cardiotônicos / Diabetes Mellitus Experimental / Cardiomiopatias Diabéticas / Anti-Inflamatórios / Miocárdio Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Relaxina / Cardiotônicos / Diabetes Mellitus Experimental / Cardiomiopatias Diabéticas / Anti-Inflamatórios / Miocárdio Idioma: En Ano de publicação: 2017 Tipo de documento: Article