title: Protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with severe acute pancreatitis.
abstract: 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-alpha 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-alpha 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-alpha 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 protective effects against intestinal mucosal injury in rats with SAP. The blockade of macrophages may provide a novel therapeutic strategy in SAP.
authors.affiliation: Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China. zhangjx@ujs.edu.cn
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Zhang
authors.forename: Sheng-Chun
authors.initials: SC
authors.lastname: Dang
authors.forename: Kai
authors.initials: K
authors.lastname: Yin
authors.forename: De-Li
authors.initials: DL
authors.lastname: Jiang
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D004002:Clodronic Acid / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018664:Interleukin-12 / Q000097:blood; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004002:Clodronic Acid; D018664:Interleukin-12; D008081:Liposomes; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha; C539355:CD68 protein, rat; D000097382:CD68 Molecule