Rabinovitch A, Suarez W L, Thomas P D, Strynadka K, Simpson I
Department of Medicine, University of Alberta, Edmonton, Canada.
Diabetologia. 1992 May;35(5):409-13. doi: 10.1007/BF02342435.
We have previously reported that oxygen free radical scavengers protect rat islet cells from damage by cytokines and we interpreted these findings as suggesting the involvement of oxygen free radicals but did not directly measure indices of free radical activity. In this study, we report on malondialdehyde, an end product of lipid peroxidation, in rat islets incubated with cytokines. The individual cytokines, interleukin 1 (1 U/ml), tumour necrosis factor (10(2) U/ml), and interferon gamma (10(2) U/ml) inhibited insulin release but did not increase islet malondialdehyde levels. Combination of these cytokines however, produced significant increases in islet malondialdehyde and this was accompanied by islet necrosis. Furthermore, an inhibitor of lipid peroxidation, U78518E, significantly decreased the cytokine-induced increase in islet malondialdehyde and protected islet Beta cells from destruction by the cytokine combination of interleukin 1, tumour necrosis factor and interferon gamma. These findings suggest that the cytotoxic action of cytokines on islet Beta cells may result from free radical production and lipid peroxidation in the islet cells.
我们之前曾报道过，氧自由基清除剂可保护大鼠胰岛细胞免受细胞因子的损伤，我们将这些发现解释为提示氧自由基的参与，但并未直接测量自由基活性指标。在本研究中，我们报告了与细胞因子一起孵育的大鼠胰岛中脂质过氧化终产物丙二醛的情况。单独的细胞因子，白细胞介素1（1 U/ml）、肿瘤坏死因子（10² U/ml）和干扰素γ（10² U/ml）可抑制胰岛素释放，但并未增加胰岛丙二醛水平。然而，这些细胞因子的组合使胰岛丙二醛显著增加，并且伴有胰岛坏死。此外，脂质过氧化抑制剂U78518E可显著降低细胞因子诱导的胰岛丙二醛增加，并保护胰岛β细胞免受白细胞介素1、肿瘤坏死因子和干扰素γ细胞因子组合的破坏。这些发现提示，细胞因子对胰岛β细胞的细胞毒性作用可能源于胰岛细胞中自由基的产生和脂质过氧化。
