title: Are gastric mucosal macrophages responsible for gastric injury in acute pancreatitis?
abstract: OBJECTIVE
  To investigate the protective effect of clodronate-containing liposomes against severe acute pancreatitis (SAP)-triggered acute gastric mucosal injury (AGMI) in rats.
  
  
  METHODS
  Clodronate- and phosphate-buffered saline (PBS)-containing liposomes were prepared by reverse-phase evaporation. The SAP rat model was established by injecting sodium taurocholate into the pancreatic subcapsular space. Sprague-Dawley rats were randomly divided into three groups: control (C), SAP plus PBS-containing liposome (P) and SAP plus clodronate-containing liposome (T). Serum tumor necrosis factor (TNF)-α levels were estimated by ELISA. Pathological changes in the gastric mucosa and pancreas were observed by hematoxylin and eosin (HE) staining. Apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The numbers of macrophages in the gastric mucosa were analyzed by CD68 immunohistochemical staining.
  
  
  RESULTS
  The liposomes had a mean diameter of 150 ± 30 nm. The TNF-α levels were significantly higher in the P group than that in the C group (2 h, 145.13 ± 11.50 vs 23.2 ± 2.03; 6 h, 245.06 ± 12.11 vs 30.28 ± 6.07, P < 0.05), and they were significantly lower in the T group than that in the P group (2 h, 93.24 ± 23.11 vs 145.13 ± 11.50; 6 h, 135.18 ± 13.10 vs 245.06 ± 12.11, P < 0.05). The pathological scores of the pancreas were lower in the T group than in the P group (2 h, 1.88 ± 0.83 vs 4.13 ± 0.83; 6 h, 2.87 ± 0.64 vs 6.25 ± 0.88, P < 0.01). The pathological scores of the gastric mucosa were also lower in the T group than in the P group (2 h, 1.12 ± 0.64 vs 2 ± 0.75; 6 h, 1.58 ± 0.53 vs 3 ± 1.31, P < 0.05). In addition, increased CD68 levels were observed in the gastric mucosa of the P group compared with the C group. Clodronate-containing liposomes decreased the CD68 levels in the mucosa of the T group. The apoptotic indexes of the gastric mucosa were higher in the T group than in the P group (2 h, 15.7 ± 0.92 vs 11.5 ± 1.64; 6 h, 21.12 ± 1.06 vs 12.6 ± 2.44, P < 0.01).
  
  
  CONCLUSIONS
  Gastric macrophages contribute to the pathogenesis of gastric injury in SAP. Clodronate-containing liposomes have protective effects against AGMI in rats with SAP.
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Sheng-Chun
authors.initials: SC
authors.lastname: Dang
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: De-Li
authors.initials: DL
authors.lastname: Jiang
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Rong-Fang
authors.initials: RF
authors.lastname: Chen
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Qu
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Xiang-Qian
authors.initials: XQ
authors.lastname: Shen
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D004002:Clodronic Acid / Q000008:administration & dosage*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020011:Protective Agents / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D013272:Stomach Diseases / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004002:Clodronic Acid; D008081:Liposomes; D020011:Protective Agents; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha; C539355:CD68 protein, rat; D000097382:CD68 Molecule
keywords: Clodronate disodium; Gastric mucosal injury; Macrophage; Pancreatitis