Effects of Octreotide on Activated Pancreatic Stellate Cell-Induced Pancreas Graft Fibrosis in Rats

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• 作者：Dan Long ; M.D.^&lowast ; ; ² ; Jun Lu ; M.D.^&lowast ; ; ² ; Lei Luo ; Ph.D.^&lowast ; ; Yingjia Guo ; Ph.D.^&lowast ; ; Chengwen Li ; Ph.D.^&lowast ; ; Wenqiao Wu ; M.D.^&lowast ; ; Juan Shan ; Ph.D.^&lowast ; ; LuLu Li ; M.D.^&lowast ; ; Shengfu Li ; M.D.^&lowast ; ; YouPing Li ; M.D.^&dagger ; ; Tao Lin ; M.D.^&Dagger ; ; Li Feng ; Ph.D.^&lowast ; ; ^{fenglily31@hotmail.com}
• 关键词：pancreas transplantation ; pancreatic stellate cells ; octreotide ; pancreatic fibrosis
• 刊名：Journal of Surgical Research
• 出版年：2012
• 期刊代码：299_00224804
• 类别：med
• 出版时间：July, 2012
• 卷：176
• 期：1
• 页码：248-259
• 文件大小：2648 K

摘要

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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.

Materials and 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聽伪-smooth muscle actin (伪-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鈥檚 trichrome staining, and immunohistochemical staining for 伪-SMA, collagen I, and tumor growth factor-尾1 (TGF-尾1) were performed.

Results

Octreotide at a concentration of >20 ng/mL significantly inhibited PSC activation and proliferation in聽vitro. Inflammatory infiltration was reduced in the octreotide group in聽vivo, and the expression levels of 伪-SMA, collagen I, and TGF-尾1 were also lower, with statistic significant difference or not. Masson鈥檚 trichrome staining showed a decrease in collagen deposition with octreotide treatment.

Conclusions

Octreotide effectively inhibits PSC activation and proliferation in聽vitro, but has a limited inhibitory effect on the development of pancreas graft fibrosis.