内,外源性生长抑素对离体培养的胰岛β细胞抗链佐霉素损伤的保护作用

在以前整体及器官水平工作的基础上,本工作进一步在离体培养的胰岛细胞上观察生长抑素(somatostatin,SS)对链佐霉素(streptozotocin,STZ)诱导的胰岛β细胞损伤的保护作用。结果表明,在向培养的胰岛细胞中加入STZ前10min,加入不同剂量(0.025,0.05和0.1μg/ml)的SS,可不同程度地保护β细胞免受STZ的破坏。给药后6h,活细胞数由STZ破坏组的41.13±0.65万个/ml分别回升到49.0±2.0,53.0±1.33和53.38±1.74万个/ml;在给药后12h,活细胞数由破坏组的46.75±0.75万个/ml,分别升为53.0±1.25,57.04±2.39和63.13±0.62万个/ml,与破坏组间均有显著差异。电镜下超微结构的观察显示,破坏组胰岛内β细胞大量死亡,胞质内正常细胞器结构消失,代之以大量空泡和颗粒状物质;胞核结构不清。而保护组的β细胞结构完整,分泌颗粒轮廓典型,高尔基复合体及线粒体结构正常。用SS抗血清中和内源性SS后再给予STZ,β细胞破坏更为严重,但重新补充SS则可翻转抗血清的效果。加入钙离子载体A_(23187),对SS的保护作用无明显影响,表明这一作用可能与Ca~(2 )机制无关。

THE PROTECTIVE EFFECT OF ENDOGENOUS AND EXOGENOUS SOMATOSTATIN ON MONOLAYER CULTURED ISLET B CELLS DAMAGED BY STREPTOZOTOCIN

Exogenous administration of somatostatin exerted a beneficial influence directly on monolayer cultured islet B cells damaged by streptozotocin (3.0 mmol/L). Six to twelve hours following the pretreatment with somatostatin of 0.025, 0.05 and 0.1 microgram/ml the number of viable cells was significantly increased from 41.13 +/- 0.65 x 10(4) cells/ml (STZ control) to 49.0 +/- 2.0, 53.0 +/- 1.33, 53.38 +/- 1.74 x 10(4) cells/ml, respectively. The ultrastructural appearance of the B cells indicated that with many vacuoles and granules occurred in the cytoplasma of these cells, normal organelles disappeared and the nuclei were obscure in structure. The pretreatment with somatostatin (0.1 microgram/ml) protected the B cells against streptozotocin, with mitochondria, Golgi's apparatus and granules in these cells intact. The destruction of B cells induced by streptozotocin was more severe after adding anti-somatostatin serum to neutralize the endogenous somatostatin in the culture, which was reversed by replenishment of somatostatin. Adding Ca2+ carrier A23187 did not change the protective effect of somatostatin, it seemed that there was no relationship between the protective effect of somatostatin and calcium mechanism.