背景:缺乏关于晚期肝硬化(LC)患者铁治疗安全性的令人信服的数据。这项研究调查了羧基麦芽糖铁的肝脏作用,静脉注射铁补充剂,在肝硬化的大鼠模型中。
方法:总共,将45只Sprague-Dawley大鼠分为三组:正常大鼠(对照组,n=15),接受静脉生理盐水的肝硬化大鼠(LC组,n=15),和肝硬化大鼠接受20mg/kg静脉铁羧基麦芽糖(LC-铁组,n=15)。通过每周两次腹膜内注射四氯化碳诱导LC。在0、2、14和28天比较生化参数。此外,在第2、14和28天,从每组5只大鼠中提取肝组织样本,以评估肝纤维化和铁沉积的程度。还比较了各组之间的炎症和氧化应激标志物。
结果:LC组和LC-铁组之间的血清丙氨酸转移酶水平在0时没有显着差异(443±110vs.444±117IU/L,P>0.99),2(453±117vs.479±136IU/L,P=0.84),14(1,535±1,058vs.1,578±711IU/L,P=0.55),或28天(2,067±641vs.2,533±914IU/L,P=0.15)。各组间肝纤维化程度相当,尽管LC-铁组的肝铁积累大于LC组。LC-铁组的炎症和氧化应激标志物水平明显低于LC组。
结论:在我们的肝硬化大鼠模型中,静脉注射铁似乎是安全的。然而,需要进一步的临床前和临床研究,以确认在LC或终末期肝病患者中静脉注射铁剂的安全性和有效性.
BACKGROUND: There is a lack of convincing data concerning the safety of iron therapy in patients with advanced liver cirrhosis (LC). This study investigated the hepatic effects of ferric carboxymaltose, an intravenous iron supplement, in a rat model of cirrhosis.
METHODS: In total, 45 Sprague-Dawley rats were allocated into three groups: normal rats (control group, n=15), cirrhotic rats receiving intravenous normal saline (LC group, n=15), and cirrhotic rats receiving 20 mg/kg intravenous ferric carboxymaltose (LC-iron group, n=15). LC was induced by twice-weekly intraperitoneal injection of carbon tetrachloride. Biochemical parameters were compared at 0, 2, 14, and 28 days. Additionally, liver tissue samples were extracted from five rats in each group at 2, 14, and 28 days for evaluation of the degrees of hepatic fibrosis and iron deposition. Inflammatory and oxidative stress markers were also compared among groups.
RESULTS: Serum alanine transferase levels did not significantly differ between the LC and LC-iron groups at 0 (443±110 vs. 444±117 IU/L, P>0.99), 2 (453±117 vs. 479±136 IU/L, P=0.84), 14 (1,535±1,058 vs. 1,578±711 IU/L, P=0.55), or 28 days (2,067±641 vs. 2,533±914 IU/L, P=0.15). The degree of hepatic fibrosis was comparable between the groups, although hepatic iron accumulation was greater in the LC-iron group than in the LC group. The levels of inflammatory and oxidative stress markers were significantly lower in the LC-iron group than in the LC group.
CONCLUSIONS: In our rat model of cirrhosis, the administration of intravenous iron appears safe. However, further preclinical and clinical studies are warranted to confirm the safety and efficacy of intravenous iron in patients with LC or end-stage liver disease.