Tohoku J. Exp. Med., 2006, 209(2)

Captopril, an Angiotensin-Converting Enzyme Inhibitor, Attenuates the Severity of Acute Pancreatitis in Rats by Reducing Expression of Matrix Metalloproteinase 9

PING CHEN, YAOZONG YUAN, SHIWEN WANG,¹ LEHENG ZHAN¹ and JIAYU XU

Department of Gastroenterology, Affiliated Ruijin Hospital of Shanghai Second Medical University, Shanghai, P.R. China, and ¹Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China

It has been reported that matrix metalloproteinase 9 (MMP-9) disrupts basement membrane and increases vascular permeability. MMP-9 therefore might participate in the pathogenesis of severe acute pancreatitis (SAP). Captopril, an angiotensin-converting enzyme inhibitor, could reduce MMP-9 expression. However, the effect of captopril on the outcome of SAP is not ascertained. The aim of this study was to determine whether captopril attenuates the severity of SAP by reducing MMP-9 expression. Thirty Sprague-Dawley rats were randomly divided into 3 groups (n = 10 for each). Rats were given intraperitoneal injection of saline (SAP group) or captopril (4 mg/kg) (treated group), and then given retrograde infusion of 5% sodium taurocholate (1.5 ml/kg) into the pancreatic duct under laparotomy to induce SAP. One group of rats, injected with saline, underwent only sham operation (Control). Experimental samples were collected at 24 hrs after the induction of SAP or sham operation. Various markers of severity of SAP, such as serum levels of amylase and trypsinogen activation peptide and the vascular permeability, were increased in rats with SAP, but were significantly decreased in captopril-treated rats (p < 0.01). Likewise, the serum MMP-9 levels and expression levels of pancreatic tissue MMP-9 were significantly higher in rats with SAP than those in captopril-treated rats and control rats (p < 0.01 for both parameters), but showed no difference between captopril-treated and control rats. These results suggest that captopril may attenuate vascular permeability by reducing MMP-9 expression in SAP, thereby ameliorating severity of the disease. The use of captopril might become a new therapeutic agent for SAP.

keywords —— matrix metalloproteinase-9; captopril; severe acute pancreatitis

© 2006 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2006, 209, 99-107

Correspondence: Yaozong Yuan, Ph.D., Department of Gastroenterology, Affiliated Ruijin Hospital of Shanghai Second Medical University, Shanghai, 200025, P.R. China.

e-mail: yyz28@medmail.com.cn