他莫昔芬对肝细胞胰岛素敏感性的影响

Effect of Tamoxifen on Hepatic Cell Insulin Sensitivity

背景：胰岛素抵抗是非酒精性脂肪性肝病（NAFLD）发生的中心环节.他莫昔芬可诱发肝脏脂肪变性,但该作用是否与胰岛素抵抗有关尚不清楚.目的：观察他莫昔芬对肝细胞胰岛素敏感性的影响并探讨其可能机制.方法：体外培养人正常肝细胞株L02,予不同浓度他莫昔芬干预24 h（联合或不联合抗氧化剂N-乙酰半胱氨酸）,加人500 ng/ml胰岛素和11.1 mmol/L葡萄糖,以葡萄糖氧化酶-过氧化物酶（GOD-POD）法检测各组葡萄糖吸收量,同时检测细胞内谷胱甘肽（GSH）和超氧化物歧化酶（SOD）水平.结果：与空白对照组相比,1、3、5 μmol/L他莫昔芬可显著抑制L02细胞对葡萄糖的吸收（P〈0.05）,作用呈浓度依赖性,并显著减低细胞内GSH和SOD水平（P〈0.05）.N-乙酰半胱氨酸能改善他莫昔芬对L02细胞葡萄糖吸收的抑制作用（P〈0.05）.结论：他莫昔芬能诱导肝细胞发生胰岛素抵抗,氧化应激可能参与其发生机制.

Insulin resistance is the pivotal mechanism for the development of nonalcoholic fatty liver disease （NAFLD）. Tamoxifen can induce hepatic steatosis, but whether this effect is associated with insulin resistance is uncertain. Aims： To investigate the effect of tamoxifen on hepatic cell insulin sensitivity and its potential mechanism. Methods： Cultured normal human hepatic cell line L02 was incubated with different dosages of tamoxifen for 24 hours in the presence or absence of antioxidant N-acetylcysteine. Then 500 ng/ml insulin and 11.1 mmol/L glucose were added to the culture media, and the absorption of glucose was measured by glucose oxidase-peroxidase （GOD-POD） method. The levels of glutathion （GSH） and superoxide dismutase （SOD） were determined simultaneously. Results： Compared with the blank controls, glucose absorption of L02 ceils was significantly reduced by 1, 3 and 5 Ixmol/L tamoxifen （P〈0.05） in a dosedependent manner, the levels of GSH and SOD were parallelly decreased （P〈0.05）. The presence of N-acetylcysteine could ameliorate the inhibition of glucose absorption induced by tamoxifen （P〈0.05）. Conclusions Tamoxifen can induce hepatic cell insulin resistance, and oxidative stress might be involved in its mechanism.