Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, Chengdu, China.
J Surg Res. 2012 Jul;176(1):248-59. doi: 10.1016/j.jss.2011.06.009. Epub 2011 Jul 5.
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.
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.
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.
Octreotide effectively inhibits PSC activation and proliferation in vitro, but has a limited inhibitory effect on the development of pancreas graft fibrosis.
在实体器官移植中，胰腺移植与移植后早期胰腺纤维化的发生率最高。活化的胰腺星状细胞（PSC）是胰腺纤维化的主要来源。奥曲肽广泛用作胰腺移植受者术后并发症的预防药物。最近的研究表明，它可以抑制肝纤维化。本研究探讨了奥曲肽对大鼠胰腺移植物纤维化的影响。
从 Sprague Dawley 大鼠中分离出 PSC，并与不同剂量的奥曲肽（1.25、2.5、5、10、20 和 40ng/ml）共培养。在 48、72 和 96 小时通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴化物评估 PSC 的增殖。通过免疫组织化学和逆转录聚合酶链反应检测 PSC 的α-平滑肌肌动蛋白（α-SMA）和胶原 I 的表达。在奥曲肽治疗（0.01mg/kg）和不治疗的情况下进行大鼠异位胰十二指肠移植。在术后第 1、3、5 和 7 天采集胰腺移植物。进行苏木精-伊红染色、马松三色染色以及α-SMA、胶原 I 和转化生长因子-β1（TGF-β1）的免疫组织化学染色。
奥曲肽浓度>20ng/ml 时可显著抑制 PSC 的体外激活和增殖。体内奥曲肽组炎症浸润减少，α-SMA、胶原 I 和 TGF-β1 的表达水平也较低，差异有统计学意义或无统计学意义。马松三色染色显示奥曲肽治疗后胶原沉积减少。
奥曲肽可有效抑制 PSC 的体外激活和增殖，但对胰腺移植物纤维化的发展抑制作用有限。
