非酒精性脂肪肝铁负荷水平调查及番茄红素干预效果和机制研究

Nonalcoholic fatty liver disease (NAFLD) patients are prone to having iron perturbations as evidenced by increasing serum ferritin level and hepatic iron overload which further increase oxidative level and aggravate hepatic damage. The mechanism of dysmetabolic iron overload in NAFLD is not clear. As a key regulator of iron metabolism, the level of hepcidin in NAFLD is contradictory. Lycopene, a carotenoid with antioxidant capacity, has been shown to quencher oxygen radicals and decrease damage of tissue. The project will compare the iron load levels of 60 NAFLD patients and 60 control objects and further examine the effect of lycopene supplementation on iron metabolism, chronic inflammation in NAFLD animal models. Then we will investigate the effect of cytokines such as IL-6 and TNF-a on hepcidin expression and the mechanism of hepatic iron overload in NAFLD. This series of investigations may shed light on the clinical guidance for NAFLD patients to prevent and control iron overload.

非酒精性脂肪肝病（NAFLD）患者易发生铁蛋白升高、肝脏铁过载等铁代谢异常，后者可进一步提高氧化应激水平，加重肝损伤。目前关于NAFLD患者易发生铁代谢异常的机制还不明确，铁调素（Hepcidin）作为铁代谢的关键调节因子，其在NAFLD患者体内的水平尚存在争议。番茄红素具有较强的抗氧化能力，可有效地清除氧自由基，减轻组织损伤。本课题拟选择60例NAFLD患者和60名对照人群分析比较铁负荷水平，采用动物实验观察番茄红素补充对大鼠铁代谢、慢性炎症反应等的改善作用，分析IL-6、TNF-α等炎性因子对hepcidin表达水平的影响，探讨NAFLD患者肝脏铁过载的可能机制。该研究预期结果可为非酒精性脂肪肝病（NAFLD）铁过载的预防和控制提供理论依据，具有一定的应用价值。

非酒精性脂肪肝病（NAFLD）患者易发生铁代谢紊乱，从而进一步促进体内氧化应激，加重肝损伤。番茄红素作为一种重要的抗氧化剂，被指出可以有效改善NAFLD患者的糖脂代谢紊乱，但是其对NAFLD患者常见的铁过载的改善效果未见报导。因此，进一步开展番茄红素补充对NAFLD铁过载的改善效果及机制研究，将为NAFLD的预防和控制提供一定的理论依据。.本课题首先采用病例对照研究，分别选取151例NAFLD患者及159例对照组人群为研究对象，对比分析其铁代谢、糖脂代谢状况、炎症水平等指标。同时采用高脂高果糖饲料喂养建立NAFLD大鼠模型，并分别在建模第1周和第5周开始给予不同剂量的番茄红素进行干预，观察番茄红素补充对NAFLD大鼠糖脂代谢、炎症水平及铁代谢紊乱的改善效果及机制。.结果显示，NAFLD患者血清铁蛋白、血红蛋白、谷丙转氨酶、血糖、血脂、尿酸、胰岛素和炎症因子（IL-6、IL-1β）水平均显著高于对照组（p值均小于0.05）。提示，NAFLD患者体内炎症水平增高，存在一定的糖脂代谢紊乱和铁过载。给予NAFLD大鼠番茄红素干预8周或12周后，可显著降低大鼠血清TG、ALT、胰岛素和IL-1β水平。同时番茄红素补充还可减轻NAFLD大鼠肝脏铁沉积，上调肝脏铁调素（Hepcidin）与铁调素调节蛋白（HJV）的基因和（或）蛋白表达水平，下调转铁蛋白受体1（TfR1）基因和蛋白表达水平。.本研究提示NAFLD患者体内存在一定程度的铁过载，番茄红素补充可有效改善NAFLD大鼠糖脂代谢紊乱和肝损伤，减轻炎症反应，对肝脏铁过载有改善作用，其机制可能与番茄红素调节肝脏铁调素、HJV及TfR1等的表达有关。本研究结果将为指导人们合理摄入番茄红素等植物化学物，预防或控制NAFLD的发生发展提供一定的理论依据。