Protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with severe acute pancreatitis

• Published in: Hepatobiliary & pancreatic diseases international Vol. 10; no. 5; pp. 544 - 551
• Main Authors: Zhang, Jian-Xin, Dang, Sheng-Chun, Yin, Kai, Jiang, De-Ii
• Format: Journal Article
• Language: English
• Published: Singapore Elsevier B.V 01.10.2011
• Subjects: Acute Disease; Animals; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Apoptosis - drug effects; clodronate; clodronate disodium; Clodronic Acid - administration & dosage; Disease Models, Animal; disodium; Endocrinology & Metabolism; Gastroenterology and Hepatology; Immunohistochemistry; In Situ Nick-End Labeling; injury; Interleukin-12 - blood; intestinal; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; intestinal mucosal injury; Liposomes; macrophage; Macrophages - drug effects; Macrophages - immunology; mucosal; Pancreas - drug effects; Pancreas - pathology; pancreatitis; Pancreatitis - blood; Pancreatitis - chemically induced; Pancreatitis - drug therapy; Pancreatitis - pathology; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Taurocholic Acid; Time Factors; Tumor Necrosis Factor-alpha - blood; macrophage; intestinal mucosal injury; pancreatitis; clodronate disodium
• ISSN: 1499-3872
• DOI: 10.1016/S1499-3872(11)60092-1

BACKGROUND: Severe acute pancreatitis (SAP) can result in intestinal mucosal injury. This study aimed to demonstrate the protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with SAP. METHODS: Liposomes containing clodronate or phosphate buffered saline (PBS) were prepared by the thin-film method SAP models were prepared by a uniform 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 (C group), a SAP plus PBS-containing liposomes group (P group) and a SAP plus clodronate-containing liposomes group (T group). At 2 and 6 hours after the establishment of SAP models, 2 mL blood samples were taken from the superior mesenteric vein to measure the contents of serum TNF-α and IL-12. Pathological changes in the intestine and pancreas were observed using hematoxylin and eosin staining, while apoptosis was detected using TUNEL staining. In addition, the macrophage markers cluster of differentiation 68 (CD68) in the intestinal tissue was assessed with immunohistochemistry. RESULTS: At the two time points, the levels of TNF-α and IL-12 in the P group were higher than those in the C group (P<0.05) Compared with the P group, the levels of TNF-α and IL-12 decreased in the T group (P<0.05). The pathological scores of the intestinal mucosa and pancreas in the T group were lower than those of the P group. In the T group, large numbers of TUNEL-positive cells were observed, but none or few in the C and P groups. The number of CD68-positive macrophages decreased in the T group.CONCLUSIONS: Clodronate-containing liposomes have prote- ctive effects against intestinal mucosal injury in rats with SAP. The blockade of macrophages may provide a novel therapeutic strategy in SAP.