J Biomed Nanotechnol. 2020 Jul 1;16(7):1082-1101. doi: 10.1166/jbn.2020.2951.
The drug octreotide, a somatostatin analog, stimulates the cellular free radical scavenging system and inhibits the release of superoxide anions from monocytes. We hypothesized that octreotide also protects islet cell function and improves the survival of transplanted islets by ameliorating the adverse effects of hypoxia and reoxygenation on these cells, thus inhibiting apoptosis. To test this hypothesis, we experimentally induced hypoxia in islet cells in mouse insulinoma Min6 cells. Octreotide treatment mildly but significantly improved cell viability under normoxic and hypoxic conditions. Secreted vascular endothelial growth factor (VEGF) from the Min6 cells was downregulated after octreotide treatment during hypoxia. By contrast, the expression of hypoxia-inducible factor (HIF)-1 was upregulated after octreotide treatment under both normoxic and hypoxic conditions. Octreotide treatment also lowered the apoptotic rate of Min6 cells under hypoxic conditions . In a mouse transplant model, octreotide improved the post-transplantation efficacy and function of islet grafts. Expression of p53 and Bax in islet grafts was upregulated in the recipients treated with octreotide one day after islet transplantation, and the octreotide-treated group produced significantly less Bax than the control group on days 3 and 7 following transplantation. TUNEL assay further demonstrated a decrease in islet cell apoptosis in the octreotide group on days 1, 3, 7, and 14 after transplantation compared with that of the control group ( 0.05). No islet cell proliferation was found in the octreotide and control groups on days 1, 3, and 7 following transplantation. However, by day 14, the group treated with octreotide demonstrated significantly higher average cell proliferation rates than the controls did ( 0.05). Thus, octreotide decreased the apoptosis of islets under hypoxic conditions and enhanced the efficacy of islet transplantation . Octreotide has excellent potential for therapeutic applications in islet transplantation and merits further study.
奥曲肽是一种生长抑素类似物，可刺激细胞自由基清除系统并抑制单核细胞中超氧阴离子的释放。我们假设奥曲肽还可以通过改善缺氧和再氧合对胰岛细胞的不良影响来保护胰岛细胞功能并提高移植胰岛的存活率，从而抑制细胞凋亡。为了验证这一假说，我们在胰岛细胞瘤小鼠胰岛素瘤 Min6 细胞中实验性诱导了细胞缺氧。奥曲肽治疗可轻度但显著提高正常氧和缺氧条件下的细胞活力。缺氧后 Min6 细胞分泌的血管内皮生长因子 (VEGF) 下调。相比之下，奥曲肽在正常氧和缺氧条件下均上调了缺氧诱导因子 (HIF)-1 的表达。奥曲肽治疗还降低了 Min6 细胞在缺氧条件下的凋亡率。在小鼠移植模型中，奥曲肽改善了胰岛移植物的移植后效果和功能。在胰岛移植后一天，接受奥曲肽治疗的受体中胰岛移植物中 p53 和 Bax 的表达上调，并且在移植后第 3 天和第 7 天，奥曲肽治疗组的 Bax 表达明显低于对照组。TUNEL 检测进一步表明，与对照组相比，奥曲肽组在移植后第 1、3、7 和 14 天的胰岛细胞凋亡减少（0.05）。在移植后第 1、3 和 7 天，奥曲肽和对照组均未发现胰岛细胞增殖。然而，在移植后第 14 天，奥曲肽治疗组的平均细胞增殖率明显高于对照组（0.05）。因此，奥曲肽可降低缺氧条件下胰岛细胞的凋亡并增强胰岛移植的效果。奥曲肽在胰岛移植中具有很好的治疗应用潜力，值得进一步研究。
