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MRI shows clodronate-liposomes attenuating liver injury in rats with severe acute pancreatitis

Hepatobiliary & Pancreatic Diseases International 2010年第2期9卷 192-200页

作者： Zhang, Jian-Xin Dang, Sheng-Chun Zhang, Yong Sha, Xin Zhang, Li-Rong Wei, Chuan-She Chen, Min Jiang, De-Li Jiangsu Univ Affiliated Hosp Dept Gen Surg Zhenjiang 212001 Peoples R China Jiangsu Univ Affiliated Hosp Dept MRI Zhenjiang 212001 Peoples R China Jiangsu Univ Sch Chem & Chem Engn Zhenjiang 212013 Peoples R China

BACKGROUND: Studies have revealed that macrophages play an important role in the development of severe acute pancreatitis (SAP). Activated macrophages can lead to a systemic inflammatory response, induce lipid peroxidation, impair membrane structure, result in injury to the liver and the other extrahepatic organs, and eventually result in multiple organ dysfunction syndrome by promoting excessive secretion of cytokines. Liver injury can further aggravate the systemic inflammatory response and increase mortality by affecting the metabolism of toxins and the release of excessive inflammatory mediators. Clodronate is a synthetic bisphosphonate, which is often used for treating bone changes caused by osteoporosis and other factors. In the current study, we created liposomes containing superparamagnetic iron oxide particles (SPIOs) for macrophage labeling and magnetic resonance imaging, using a novel method that can bind the clodronate to induce apoptosis and deplete macrophages. METHODS: Superparamagnetic Fe(3)O(4) nanoparticles were prepared by chemical coprecipitation. SPIO-containing liposomes and SPIO-clodronate-containing liposomes were prepared by the thin film method. SAP models were prepared by injection of sodium taurocholate (2 ml/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group, a SAP plus SPIO-liposome group, and a SAP plus SPIO-clodronate-containing group. Two and six hours after SAP models were available, T2-weighted MRI scans (in the same plane) of the livers of rats in each group were performed. At the end of the scans, 2 ml of blood was taken from the superior mesenteric vein to measure the levels of serum amylase, ALT, AST, TNF-alpha, and IL-6. Pathological changes in the liver and pancreas were assessed. RESULTS: Transmission electron microscopy showed that the liposomes had a uniform size. No pathological changes in the pancreata of rats in the control group were noted. The pat

关键词： pancreatitis, acute clodronate disodium liver injury MR imaging macrophage

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