半乳糖血症的病患會出現一些肝臟病癥，像是血液中的半乳糖升高、黃疸、肝腫大、肝功能試驗異常和脂肪肝。研究顯示體內累積過多的半乳糖會增加肝臟內活性氧化物質和干擾肝臟的待謝途徑。 我們假定半乳糖引起的活性氧化物質堆積在半乳糖血症病患的肝臟病癥中扮演重要角色。因此，本研究將探討半乳糖引起的活性氧化物質對於肝臟損傷和脂肪代謝的影響；並且探討以抗氧化物N-乙醯半胱胺酸(NAC)治療是否能回復半乳糖造成的改變。 肝細胞AML12培養在含有不同比例的葡萄糖和半乳糖培養基中，以18 mM葡萄糖培養基的作為控制組，與11.5 mM葡萄糖加6.5 mM半乳糖、5 mM 葡萄糖加13 mM半乳糖、5 mM葡萄糖比較。動物實驗方面，以管餵的方式給予C57BL/6小鼠連續60天的500 mg/Kg半乳糖，500 mg/Kg半乳糖加上200 mg/Kg的N-乙醯半胱胺酸，控制組則給予生理食鹽水。結果發現細胞培養在含有半乳糖的培養基中，會使細胞存活率減少、粒線體超氧化物增加，以及減少AMPK的磷酸化；細胞內的三磷酸腺苷、有氧呼吸作用和PGC1-α和SREBP-1蛋白表現量則沒有改變。 在活體實驗中，餵食半乳糖的小鼠體重下降，從組織切片可以看出有明顯的脂肪堆積在肝臟中，肝臟組織中的三酸甘油酯傾向上升且SREBP-1的表現量有增加的傾向。而給予N-乙醯半胱胺酸的治療能夠回復半乳糖引起的肝臟三酸甘油酯增加和組織切片中的脂肪堆積。總結來說，我們的研究顯示半乳糖會藉由增加氧化壓力和脂肪生成而造成脂肪肝，而給予N-乙醯半胱胺酸的治療可以有效的減緩肝臟的脂肪堆積。

Galactosemia patients present many symptoms such as elevated galactose level in blood, jaundice, hepatomegaly, abnormal liver function tests and fatty liver. Excess galactose was reported to induce reactive oxygen species (ROS) and disturb metabolic pathways in liver. We hypothesized that galactose-induced ROS played an important role in liver disorders in galactosemia. Therefore, this study was aimed to examine the effects of galactose-induced ROS on liver injuries and fat metabolism, and to investigate whether N-acetyl cysteine (NAC) would alleviate these changes. AML12 hepatocytes were cultured in DMEM/F12 medium with different ratio of glucose and galactose, including 18 mM glucose, 11.5 mM glucose plus 6.5 mM galactose, 5 mM glucose plus 13 mM galactose and 5 mM glucose. C57BL/6 mice were given 500 mg/Kg galactose and 500 mg/Kg galactose plus 200 mg/Kg NAC for 60 days by oral gavage. The results showed that galactose-containing culture medium resulted in decreased cell viability, increased mitochondrial superoxide and reduced AMPK phosphorylation in AML12 cells. The protein expression of PGC1-α and SREBP-1, oxygen consumption rate, ATP content were not altered in hepatocytes grown with galactose. In addition, in vivo studies showed decreased body weight and remarkable lipid accumulation in the liver of galactose-treated mice, along with increased liver TG and SREBP-1 expression. The NAC treatment diminished liver TG content and histological fatty change caused by galactose administration. In conclusion, galactose-induced liver steatosis through increased oxidative stress in mice hepatocytes, and NAC treatment could alleviate the lipid accumulation in liver.

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