Protective effect of intermedin on myocardial cell in a rat model of severe acute pancreatitis.
Protective effect of intermedin on myocardial cell in a rat model of severe acute pancreatitis.
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DOI：
10.2478/s11658-011-0020-1
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发表时间：
2011-09
影响因子：
8.3
通讯作者：
Xia Q
中科院分区：
文献类型：
--
作者：
Du X;Cao Y;Xue P;Lin Z;Zeng Z;Xia Q
重症急性胰腺炎（SAP）是一种常见病，预后差。心力衰竭是SAP患者死亡的原因之一。中介素（IMD）是一种有效的内源性心脏保护物质。外源性IMD的管理显示出有益的效果，在心血管疾病。本研究的目的是研究SAP的心肌损害，并确定IMD对SAP的治疗潜力。使用SAP大鼠模型，我们研究了SAP诱导后内源性IMD的表达，并确定IMD对心肌功能，组织学形态，心肌梗死相关基因表达和预后的影响。结果表明，SAP大鼠心功能和组织结构明显受损。外源性IMD可明显保护心功能，改善心肌损伤。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）显示，心肌细胞凋亡是广泛存在于SAP大鼠，IMD输注导致的表达增加的促生存因子Bcl-2，但减少促凋亡因子Bax和caspase-3。此外，IMD灌注还逆转了SAP大鼠心脏组织IMD受体系统的变化。此外，我们发现IMD输注大大降低了SAP大鼠的死亡率。总之，SAP通过调节凋亡和促生存基因表达，抑制心肌细胞凋亡，保护心脏功能，对SAP产生治疗作用，并为IMD治疗人重症急性胰腺炎的临床试验提供了见解。可通过10.2478/s11658-011-0020-1获取本文的补充材料，授权用户可访问。
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. Supplementary material is available for this article at 10.2478/s11658-011-0020-1 and is accessible for authorized users.