东大学子发现去铁制剂治疗非酒精性脂肪肝新机制

2017-09-28 佚名 央广网

铁是细胞生长所需的基本元素,但是铁过量也会导致机体的损害,而铁离子螯合剂可以显着影响细胞内外的铁水平,在临床上多用于治疗人体铁元素过载带来的各种疾病。日前,东大学子通过实验研究发现,铁螯合剂去铁敏(DFO)对非酒精性脂肪肝具有明确的减轻作用,在减少动物血脂等方面意义重大,为临床治疗非酒精性脂肪肝等脂类代谢紊乱相关疾病提供了理论依据。

铁是细胞生长所需的基本元素,但是铁过量也会导致机体的损害,而铁离子螯合剂可以显着影响细胞内外的铁水平,在临床上多用于治疗人体铁元素过载带来的各种疾病。日前,东大学子通过实验研究发现,铁螯合剂去铁敏(DFO)对非酒精性脂肪肝具有明确的减轻作用,在减少动物血脂等方面意义重大,为临床治疗非酒精性脂肪肝等脂类代谢紊乱相关疾病提供了理论依据。

非酒精性脂肪肝是一种无过量饮酒史、以肝细胞脂肪变性和脂质贮积为特征的临床病理综合征。流行病学调查显示,在我国,约有30%的成人患有此症。研究表明,非酒精性脂肪肝患者的血清铁水平增加,肝脏铁染色阳性反应增强,此症与心血管疾病,肝脏及其他肿瘤相关的死亡率增加密切相关。


经典铁螯合剂DFO主要应用于治疗重型地中海贫血等铁负荷疾病,已经临床安全应用几十年。东北大学生命科学与健康学院本科生创新团队薛晗等同学,在教师郭闯的指导下应用DFO对ob/ob糖尿病(肥胖、暴饮暴食引起)模型小鼠进行腹腔注射处理,首次证实铁螯合剂对非酒精性脂肪肝变性有明确的减轻作用,减少特定组织铁离子是改善ob/ob肥胖小鼠肝脂肪变性的有效办法。

据薛晗介绍,实验数据证明,铁螯合剂可减少肝组织的铁沉积,降低氧化应激水平,同时上调脂代谢相关蛋白的表达水平,维持肝脏脂代谢及铁代谢的稳态,进而改善肝脏脂肪变性。与此同时,铁螯合剂能够抑制炎症细胞因子的产生以及肝细胞的凋亡,上调缺氧诱导因子-1及其调控的相关适应性蛋白的表达水平,增加肝组织的适应、再生能力,从而为将铁螯合剂“老药新用”临床治疗2型糖尿病和非酒精性脂肪肝等相关疾病提供了新视点。

据悉,减少膳食中的铁含量、放血疗法等去铁对治疗非酒精性脂肪肝虽然十分有效,但这两种办法难以准确控制,让普通患者难以接受,因此大规模的推广受到限制。而由于铁螯合剂DFO已经临床安全应用几十年,其在减少动物血脂及肝脂肪变性方面具有显着作用,可作为一种相对安全又高效的药物加以推广,有快速转入临床应用的潜力。

参考文献:

1.Xue, H., et al., Deferoxamine ameliorates hepatosteatosis via several mechanisms in ob/ob mice. Ann N Y Acad Sci, 2016. 1375(1): p. 52-65.

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