title: Effects of octreotide on activated pancreatic stellate cell-induced pancreas graft fibrosis in rats.
abstract: BACKGROUND
  Of solid organ transplantations, pancreas transplantation is associated with the highest incidence of pancreatic fibrosis in the early post-transplantation period. Activated pancreatic stellate cells (PSCs) are the main source of pancreatic fibrosis. Octreotide is widely used as a prophylactic for postoperative complications in pancreas transplant recipients. Recent studies have shown that it can inhibit liver fibrosis. This study investigated the effect of octreotide in pancreas graft fibrosis in rats.
  
  
  METHODS
  Isolated PSCs from Sprague Dawley rats were co-cultured with different doses of octreotide (1.25, 2.5, 5, 10, 20, and 40 ng/mL). PSC proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide at 48, 72, and 96 h. The α-smooth muscle actin (α-SMA) and collagen I expressions of PSCs were detected by immunohistochemistry and reverse-transcriptase polymerase chain reaction. Rat heterotopic pancreaticoduodenal transplantation was performed with and without octreotide treatment (0.01 mg/kg). Pancreas grafts were harvested at postoperative d 1, 3, 5, and 7. Hematoxylin-eosin staining, Masson's trichrome staining, and immunohistochemical staining for α-SMA, collagen I, and tumor growth factor-β1 (TGF-β1) were performed.
  
  
  RESULTS
  Octreotide at a concentration of >20 ng/mL significantly inhibited PSC activation and proliferation in vitro. Inflammatory infiltration was reduced in the octreotide group in vivo, and the expression levels of α-SMA, collagen I, and TGF-β1 were also lower, with statistic significant difference or not. Masson's trichrome staining showed a decrease in collagen deposition with octreotide treatment.
  
  
  CONCLUSIONS
  Octreotide effectively inhibits PSC activation and proliferation in vitro, but has a limited inhibitory effect on the development of pancreas graft fibrosis.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, Chengdu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Guo
authors.forename: Chengwen
authors.initials: C
authors.lastname: Li
authors.forename: Wenqiao
authors.initials: W
authors.lastname: Wu
authors.forename: Juan
authors.initials: J
authors.lastname: Shan
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.forename: Shengfu
authors.initials: S
authors.lastname: Li
authors.forename: Youping
authors.initials: Y
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Feng
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D066298:In Vitro Techniques; D008297:Male; D023421:Models, Animal; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology*; D016035:Pancreas Transplantation / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D015282:Octreotide; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat