當歸補血湯對鐵吸收之影響

The Influence of Danggui Buxue Tang on Iron Absorption

陳詩瑜(Shih-Yu Chen)

指導教授 ： 王靜瓊

臺北醫學大學/藥學院/生藥學研究所/碩士(2010年)

https://doi.org/10.6831/TMU.2010.00235

摘要

缺鐵性貧血為貧血分類中盛行率最高的疾病，造成缺鐵性貧血的原因有鐵吸收不良、攝鐵不足、失血過多等，在醫療發達的現今缺鐵性貧血仍是急待解決的問題；而當歸補血湯組成為當歸及黃耆，是傳統醫學之補氣生血方劑。因此本研究利用當歸補血湯與鐵併用治療缺鐵性貧血，以探討古籍上所稱「補血」，是否與治療缺鐵性貧血有關，並觀察當歸補血湯與鐵劑，中西藥合併使用之療效。

首先利用Caco-2細胞攝鐵模式，檢測當歸補血湯使鐵蛋白(ferritin)生合成之影響，結果顯示：當歸及黃耆單獨使用不會增強鐵蛋白形成，而當歸補血湯則具劑量依存性的促使鐵蛋白形成，且其指標成分阿魏酸(ferulic acid)亦具有促進鐵吸收之作用。繼而探討當歸補血湯與鐵合併使用及間隔使用探討當歸補血湯對鐵吸收之影響，結果顯示：當歸補血湯與鐵併用時，當歸補血湯對於鐵吸收有抑制作用，與鐵間隔使用時則顯著具促進鐵吸收之作用；最後再以大鼠血紅素再生法探討體內之療效，結果顯示當歸補血湯與鐵經口服併用也會抑制鐵之吸收，而當歸補血湯本身即具促使血紅素上升之作用，且由血紅素再生率(HRE)可得知當歸補血湯中的鐵含量為37.6 mg/g，其生體可用率高達1947%。

利用植物化學成分分析發現，當歸補血湯中含酚類化合物(6.51 mg/g)、縮合型丹寧化合(2.31 mg/g)及皂苷類化合物(34.48 mg/g)；而由總二價鐵分析結果中，鐵與當歸補血湯反應後之二價鐵含量減少，推測當歸補血湯中成分如酚類、縮合型丹寧與鐵形成不溶性沉澱物而阻礙鐵吸收。另外，以西方點墨法分析蛋白質表現，亦發現當歸補血湯可以活化DMT-1蛋白質表現量，推測其為促使鐵吸收增強的機轉。

綜合結果：當歸補血湯單獨使用時，利用在體內、外試驗，皆顯示其具促進鐵儲存利用之作用，顯示當歸補血湯可應用於缺鐵性貧血患者。但當歸補血湯與鐵劑同時服用時，會抑制鐵之吸收，若間隔使用，則可增強鐵之吸收。因此建議當歸補血湯要與鐵劑合併治療缺鐵性貧血時，要先服用當歸補血湯活化DMT-1，再服用鐵劑會使鐵劑吸收之效果增強。

關鍵字

當歸補血湯 ； 鐵 ； 鐵蛋白 ； Caco-2 ； 血紅素濃度再生率

並列摘要

Iron deficiency anemia, the most common type of anemia, is caused by reasons such as iron malabsoption, iron-deficient diet, and blood loss. The traditional Chinese medicine, Danggui Buxue Tang (DBT), containing Radix angelicae sinensis (Danggui) and Radix astragali (Huangqi) has been used to invigorate “Qi” and nourish “Blood”. In this study, DBT was combined with iron to treat iron deficiency anemia. Another objective was to delineate whether the “nourish the blood”, as described in the ancient medicine books, were related to the iron deficient anemia treatment or not.

In the first place, Caco-2 cell iron uptake model was used to detect the effect of ferritin biosynthesis. The results showed that Danggui and Huangqi could not enhance ferritin biosynthesis, but DBT could significantly promote ferritin biosynthesis. The principle constituent of DBT, ferulic acid, also could enhance iron absorption. The treatment program of DBT and iron in Caco-2 cells were exchanged to know the interaction of DBT and iron. The results revealed while Caco-2 cells were co-treated with DBT and iron, DBT could inhibit the absorption of iron. When DBT or iron was pre-treated, DBT could significantly enhance the absorption of iron. Therefore, the rat hemoglobin repletion assay was used to explore the above therapeutic activity in vivo. The result showed that the absorption of iron was reduced after co-treatment with DBT and iron in Wistar rats. However, the hemoglobin level was increased in the DBT group. The bioavailability of the iron was increased up to 1947% in DBT group in the hemoglobin repletion efficiency (HRE) test.

The results of phytochemical analysis revealed that there are phenol compounds (6.51mg/g), condensed tannins (2.31mg/g), and saponins compounds (34.48mg/g) in DBT. In addition, the total ferrous content was decreased in the mixture of DBT and iron, indicating of that certain components of DBT like phenols, condensed tannins could chelate the iron. Besides, DBT could activate the DMT-1 expression in Caco-2 cells by Western blotting assay. Therefore, we assumed the iron promoting absorption of DBT was mediated through the activation the DMT-1 in Caco-2 cells.

In conclusion, the DBT enhanced the bioavailability of the iron both in vitro and in vivo. The absorption of iron was inhibited by DBT and iron co-treatment, but enhanced by DBT and iron pre-treatment. Based on the above results, we suggested DBT and iron should be administrated separately for iron deficient anemia patients.

並列關鍵字

Danggui Buxue Tang ； iron ； ferritin ； Caco-2 ； hemoglobin repletion efficiency

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