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Protective effect of intermedin on myocardial cell in a rat model of severe acute pancreatitis

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Abstract

Severe acute pancreatitis (SAP) is a common disease with a poor prognosis. Heart failure is one cause of SAP patient death. Intermedin (IMD) is a potent endogenous cardio-protective substance. Administration of exogenous IMD showed beneficial effects in cardiovascular diseases. The aim of this study was to investigate the myocardial damage in SAP and to determine the therapeutic potential of IMD for SAP. Using an SAP rat model, we examined endogenous IMD expression following SAP induction, and determined the effect of IMD on myocardial function, histological morphology, apoptosis-related gene expression, and prognosis. Our results indicated that the cardiac function and histological structure were significantly disrupted in SAP rats. Infusion of exogenous IMD significantly preserved cardiac function and ameliorated myocardial damage. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) revealed that myocardial apoptosis was extensively present in SAP rats, and IMD infusion led to increased expression of the prosurvival factor Bcl-2, but decreased pro-apoptotic factors Bax and caspase-3. In addition, IMD infusion also reversed the change of IMD receptor systems in SAP rat heart tissue. Furthermore, we found that IMD infusion greatly decreased mortality of SAP rats. In conclusion, administration of SAP produced therapeutic effects in SAP through modulating apoptotic and pro-survival gene expression, inhibiting myocardial apoptosis, preserving cardiac function, and a useful therapeutic agent for SAP, and provides us an insight for a clinical trial of IMD for treating human severe acute pancreatitis.

Abbreviations

ADM:

adrenomedullin

CGRP:

calcitonin gene-related peptide

CL:

calcitonin receptor-like receptor

IMD:

intermedin

MODS:

multiple organ dysfunction syndrome

RAMP:

receptor-activity-modifying protein

SAP:

severe acute pancreatitis

TUNEL:

terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling

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Correspondence to Zhi Zeng.

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Key words

  • Severe acute pancreatitis
  • Myocardial damage
  • Apoptosis
  • Intermedin treatment