目的 探讨血管内皮损伤与铁调素(hepcidin)高表达的相关性, 以及川芎嗪对其的干预作用。方法 24只SD大鼠随机分为4组:对照组、模型组、肝素阳性对照组(肝素组)及川芎嗪组, 每组6只。对照组大鼠以普通饲料喂养, 其余3组以高脂饲料喂养。8周后, 对照组及模型组大鼠ip给予生理盐水2 mL/kg, 肝素组ip给予肝素钠注射液5 mg/kg, 川芎嗪组ip给予盐酸川芎嗪注射液40 mg/kg, 均连续给药7 d。大鼠腹主动脉取血后分离血清, 检测各组大鼠血脂指标, 检测血清铁调素、一氧化氮(NO)、内皮素1(ET-1)、活性氧(ROS)、丙二醛(MDA)、过氧化氢酶(CAT)及超氧化物歧化酶(SOD)水平;截取主动脉组织, 进行铁含量检测及组织病理学观察。结果 与对照组比较, 模型组大鼠血清铁调素、ET-1、ROS、MDA水平均升高(P<0.05、0.01), 而NO、SOD及CAT水平均降低(P<0.05、0.01);主动脉内铁含量明显升高(P<0.01), 且主动脉组织出现了内膜损伤。与模型组比较, 肝素组和川芎嗪组大鼠血清铁调素、ET-1、ROS、MDA水平均显著降低(P<0.05、0.01), NO及CAT水平均显著升高(P<0.01), SOD水平有升高趋势;主动脉组织内铁含量均降低(P<0.05、0.01), 且主动脉组织内膜损伤有所减轻。结论 内皮损伤程度加重的同时铁调素呈高表达状态, 应用川芎嗪后, 内皮损伤减轻, 铁调素水平下降, 说明川芎嗪对内皮的保护作用可能与其对铁调素高表达的抑制有关。

Objective To explore the correlation between the high expression of hepcidin and vascular endothelial damage and the intervention effect of tetramethylpyrazine (TMP). Methods Twenty-four SD rats were randomly divided into four groups: blank control, model, heparin, and TMP groups. Except the rats in the blank control group, the rats in all other groups were fed with high-fat diet for 8 weeks. The rats in the blank control and model groups were injected with normal saline at 2 mL/(kg·d). The rats in the TMP group were injected with TMP at 40 mg/(kg·d), and heparin at 5 mg/(kg·d) was given to those in the heparin treated group. After rats were given medicine for 7 d, the levels of blood lipid, serum hepcidin, NO, ET-1, ROS, MDA, CAT, and SOD were detected. Results As compared with blank control group, the levels of hepcidin, ET-1, ROS, and MDA in serum were significantly increased in the model group (P < 0.05), while NO, CAT, and SOD were obviously decreased (P < 0.05). Compared with the model group, the levels of hepcidin, ET-1, ROS, and MDA in serum were obviously decreased in TMP and heparin groups (P < 0.05), while NO and CAT were obviously increased (P < 0.05). Conclusion Hepcidin expression is increased with the vascular endothelial damage aggravated. After rats are given TMP, the level of serum hepcidin and extent of vascular endothelial damage are decreased. It is suggested that TMP has the protective effects on the vascular endothelial function might be correlated to inhibiting high expression of hepcidin.

国家自然科学基金资助项目(81102845);2013年甘肃高校"飞天学者特聘计划"项目