营养强化剂纳米铁脂质体吸收与补铁机制研究

Iron is essential for a large number of biological processes. Therefore, iron acquisition is a fundamental requirement in almost all living organisms. Iron deficiency anemia is the most common form of anemia in the world. Sports training can lead iron metabolism-regulating hormones (hepcidin) up-regulation. It is followed by the iron exporter ferroportin 1(FPN1) down-regulation. Result in lower absorption of iron, makes the body unable to obtain iron supplement, eventually causing movement of iron-deficiency anemia. Iron deficiency anemia is one of the important factors affecting players ' physical fitness and exercise. Regular iron supplement absorption is low, and stimulates the gastrointestinal tract, there is nausea, vomiting, diarrhea and other side effects. How to increase iron absorption in vivo bioavailability and is non-toxic and nutritional intervention has become the bottleneck problem of the iron compound sport nutrition for exercise-associate anemia. Iron liposome is prepared with ferric citrate, heme iron which is used as food additive by nanotechnology, respectively. The product would be nano-liposome, which is high absorption and high bioavailability and iron high security. Its regulation of absorption and pharmacokinetics would be explained. The result would provide the theoretical basis to the design of the effective iron supplements and the nutrition intervention on sports anemia.

缺铁性贫血是国内外最常见的贫血，运动训练容易造成铁代谢中枢分子铁调节激素（hepcidin）表达上调，造成膜铁转运蛋白 (Ferroportin 1，FPN1)下调，导致铁的吸收下降，最终造成缺铁性运动性贫血，从而影响运动员体能和运动状态的重要原因之一。膳食中强化铁是营养干预缺铁性贫血最为简单的方法，但是现有的无机铁强化剂吸收利用率较低，且刺激胃肠道，出现恶心、呕吐、腹泻等副反应。因此如何提高铁的体内吸收与生物利用率且无毒已成为营养干预运动型贫血的瓶颈性问题。本课题拟利用纳米技术对铁营养强化剂-柠檬酸铁和血红素铁进行脂质体化，获得高吸收、高生物利用率且安全性高的纳米铁脂质体，获得其吸收与代谢动力学规律，为铁营养强化补剂的有效设计及在运动性贫血中的营养干预提供理论基础。

本研究中我们运用旋转蒸发薄膜-超声法制备了血红素铁脂质体和柠檬酸铁脂质体，并对这两种脂质体的包封率、微观结构、粒径分布和zeta电位等物理指标进行了测定，结果表明这两种脂质体均有较为稳定的物理性质。用这两种铁脂质体分别对炎症型贫血模型大鼠进行灌胃，结果发现用柠檬酸铁脂质体灌胃大鼠中的血清铁比用柠檬酸铁灌胃大鼠的血清铁浓度提高了119%，而用血红素铁脂质体灌胃大鼠的血清铁浓度比用血红素灌胃大鼠的血清铁浓度提高了54%。另外，这两种铁脂质体均可上调铁调素（hepcidin）的表达，血红素铁脂质体的上调作用更为明显，铁调素是机体内一种重要的铁调节因子。并对柠檬酸铁脂质体在SD大鼠体内的药动学及其在组织中的分布规律，比较其与柠檬酸铁的组织分布差异，同时对其体内吸收、分布过程进行了系统的研究，以期为其临床应用和制剂设计提供依据。所有试验结果都表明用铁脂质体补充机体铁的效果均优于单纯的铁制剂。因此，铁脂质体有望被用于铁强化食品来治疗缺铁性贫血，尤其是炎症性贫血。