Kasuga A, Nakaki T, Takei I, Takayama S, Ozawa Y, Maruyama T, Miyazaki J, Saruta T
Department of Internal Medicine, Keio University, School of Medicine, Tokyo, Japan.
Endocr J. 1995 Apr;42(2):259-63. doi: 10.1507/endocrj.42.259.
Macrophages from recent onset non-obese diabetic (NOD) mice showed cytotoxicity against the NOD mouse derived beta-cell line, MIN6N-9a. In this report, we examined whether nitric oxide is associated with beta-cell destruction. Peritoneal exudate cells (PEC), obtained from cyclophosphamide treated NOD mice showed higher cytotoxicity against MIN6N-9a compared to PECs from saline injected NOD mice (P < 0.01). This effect was suppressed in cells incubated with 0.5 mmol/l NG-methyl-L-arginine, a nitric oxide synthase inhibitor (P < 0.001). In addition, the nitrite concentration of the co-culture medium, as an index of nitric oxide production, increased in MIN6N-9a cells co-cultured with peritoneal exudate cells from cyclophosphamide injected NOD mice but not in co-culture with saline injected NOD mice (P < 0.05). Thus, nitric oxide plays an important role in beta-cell line destruction of macrophages obtained from NOD mice.
近期发病的非肥胖型糖尿病（NOD）小鼠的巨噬细胞对源自NOD小鼠的β细胞系MIN6N-9a表现出细胞毒性。在本报告中，我们研究了一氧化氮是否与β细胞破坏有关。与注射生理盐水的NOD小鼠的腹膜渗出细胞（PEC）相比，从经环磷酰胺处理的NOD小鼠获得的腹膜渗出细胞对MIN6N-9a表现出更高的细胞毒性（P < 0.01）。在与0.5 mmol/l NG-甲基-L-精氨酸（一种一氧化氮合酶抑制剂）孵育的细胞中，这种效应受到抑制（P < 0.001）。此外，作为一氧化氮产生指标的共培养基中亚硝酸盐浓度，在与注射环磷酰胺的NOD小鼠的腹膜渗出细胞共培养的MIN6N-9a细胞中增加，但在与注射生理盐水的NOD小鼠共培养时未增加（P < 0.05）。因此，一氧化氮在NOD小鼠巨噬细胞的β细胞系破坏中起重要作用。
