当归补血汤通过调节细胞铁代谢关键环节改善妊娠期铁缺乏的机理研究

Trace element iron is essential for nearly all living organisms. It is the key component of iron-containing enzymes and proteins，which participate in many cellular biological processes. It is estimated that nearly one quarter of population worldwide has been suffered from anemia due to iron deficiency. Anemia is the common complication of pregnancy，it is one of the high risk gestations. Iron-deficiency anemia（IDA）is the most common，it can result in severe adverse pregnancy outcomes，and can destroy infant’s psychomotor and intellectual growth. The results show that the incidence of iron deficiency in Pregnancy and Iron-deficiency anemia is high at present. It's immediacy to pay attention to iron deficiency in Pregnancy. In normal physiological status，maintenance of iron homeostasis is crucial. It is believed that iron is uptake by small intestine, stored in liver，transported in blood，recycled by macrophages, and finally utilized by cells to fulfill the functions. In this study，we follow TCM theory of“supplementing qi and nourishing blood”and clinical effect，the hypothesis of Danggui Buxue Decoction maintenance of iron homeostasis by cellular iron metabolism regulating is put forward.We try to reveal the molecular mechanism of Dang gui Buxue Decoction maintenance of iron homeostasis，fill the gaps of this research field. So can provide theoretical basis of improve dietary structure、carry forward the Homologous Culture of Medicine and Food、 promote clinical medicine towards preventive medicine

铁是机体必需微量元素，参与机体合成血红蛋白、肌红蛋白及多种酶的组成和功能发挥，对维持生命和健康至关重要。近四分之一的世界人口遭受铁缺乏或缺铁性贫血的威胁。贫血是妊娠期常见并发症，属高危妊娠范畴。缺铁性贫血最为常见，可导致严重的不良妊娠结局及婴儿精神运动和智力发育受损。研究表明，现阶段中国孕妇铁缺乏和缺铁性贫血发病率高，关注妊娠期铁缺乏刻不容缓。正常生理状态下，机体通过非常复杂的体系调控和维持自身铁稳态。在这一过程中，细胞铁代谢发挥了重要作用，包括小肠细胞铁代谢、体细胞铁代谢、巨噬细胞介导的“铁再循环”。本项目遵循中医“补气养血”理论，从临床疗效出发，提出中医古籍名方“当归补血汤”“通过调节细胞铁代谢实现铁稳态”的科学假说，通过实验揭示其影响细胞铁代谢关键环节改善妊娠期铁缺乏的分子机制，填补这一领域研究空白，为改善膳食结构、药食同源，推动临床医学走向预防医学提供理论依据。

铁是人体必需的微量元素之一，妊娠期铁缺乏和缺铁性贫血对孕产妇及婴幼儿均可造成较大损害，导致严重的不良妊娠结局及婴儿精神运动和智力发育受损。中国孕妇铁缺乏和缺铁性贫血罹患率高，严重影响母婴健康，已成为重要的公共卫生课题。本课题以中医“补气生血”理论为指导，从临床疗效出发，提出中医古籍名方“当归补血汤”“通过调节细胞铁代谢实现铁稳态”的科学假说，通过实验揭示其影响细胞铁代谢关键环节改善妊娠期铁缺乏的分子机制，丰富中医补气养血、小肠泌别清浊、肝藏血、心主血脉、肾主髓，化生血液、“肾生骨髓，髓生肝”、“骨髓坚固，气血皆从”等理论的科学内涵。为改善膳食结构、弘扬药食同源文化，推动临床医学走向预防医学提供理论依据。研究手段采用动物造模法，低铁饲料喂养幼鼠，4周后造成缺铁性贫血大鼠模型，合笼交配分组，成功建立Wistar大鼠妊娠期缺铁性贫血模型，分别给予药物处理至产后21天仔鼠断乳，抽血、处死，获取各组模型动物小肠、肝脏、心脏等生物样本，免疫组化法检测各组大鼠肝脏细胞TfR1（转铁蛋白受体1）、TfR2（转铁蛋白受体2）的表达；小肠细胞FPN1（膜铁转运蛋白1）、HP（膜铁转运辅助蛋白）的表达。初步数据显示，造模成功，缺铁性贫血组大鼠造模前后活动量、精神、毛发、耳廓脚趾色泽、体重均有显著变化；HGB、RBC、HCT、MCB、MCHC等血液学指标模型组均明显低于正常对照组；经当归补血汤联合元素铁处理后，各治疗组血液学指标比对照组均有显著升高。免疫组化显示，各治疗组小肠细胞上FPN1、HP蛋白表达、肝脏细胞TfR1、TfR2的表达均比模型组低，显著改善妊娠期缺铁性贫血铁代谢紊乱，促进铁吸收，改善妊娠期缺铁性贫血。