高浓度芬太尼抑制体外培养大鼠胰岛葡萄糖刺激胰岛素分泌

High concentration fentanyl inhibits glucose-evoked insulin release in rat pancreatic islets in vitro

目的研究高浓度芬太尼对大鼠胰岛的损伤作用。方法通过用胶原酶V液灌注分离成年SD大鼠胰岛,不连续密度梯度离心法纯化胰岛。然后将胰岛分为空白对照组和处理组,处理组与20 ng/ml的芬太尼在静态条件下共同培养24 h和后,检测低高浓度葡萄糖(2.8和16.7 mmol/L)刺激胰岛素释放试验,细胞内cAMP及蛋白含量,电子显微镜检测胰岛细胞。结果高浓度的芬太尼明显抑制大鼠胰岛的葡萄糖刺激胰岛素释放量,及细胞内cAMP的含量,电子显微镜检测显示高浓度芬太尼对大鼠胰岛具有损伤作用。结论高浓度芬太尼抑制体外培养大鼠胰岛素的分泌,并且对鼠胰岛细胞具有一定的损伤作用。

Objective To explore the harmful effect of high concentration fentanyl on rat＇ s pancreatic islets. Methods Rat pancreatic islets were isolated from the pancreas by common bile duct intraductal collagenaseV digestion and purified by discontinuous Ficoll density gradient centrifugation. The islets were divided into two groups： the control group and test group. In the test group, the islets were co-cultured with 30 ng/ml fentanyl for 48 h under static conditions. Insulin release in response to low and high concentrations （2. 8 and 16. 7 mmol/L, respectively ） of glucose, cell cAMP and protein contents were measured. Morphological assessment was accomplished by electron microscopy. Results Low- and high-glucosestimulated insulin release and cAMP in the control group were significantly higher than those in test group （1.276 ±0.112） ng/mlvs. （0.788± 0.091） ng/ml, （2.124 ± 0.181） ng/mlvs. （1.391 ± 0.156） ng/ml, and （ 19. 259 ± 3. 628 ） pmol/ml vs （ 12.983 ± 3. 328 ） pmol/ml, respectively, （ P 〈 0.05 ）.Electron microscopy studies showed that the islets were damaged by 30 ng/ml fentanyl. Conclusion Higher concentration of fentanyl significantly inhibits glucose-stimulated insulin release from rat islets and severely damages β-cells of pancreatic in rats islets.