不同膳食鐵量補充對缺鐵貧血大鼠肝臟鐵調節蛋白活性之影響

Different Degrees of Dietary Iron Repletion on the Hepatic Iron Activities and Regulatory Proteins in Iron Deficiency Anemic Rats

何素珍(Su-Chen He) ； 蕭寧馨(Ning-Sing Shaw)

《中華民國營養學會雜誌》 25卷1期 (2000/03) Pp. 17-28

https://doi.org/10.6691/JCNS.200003_25(1).0003

摘要

鐵調節蛋白（iron regulatory proteins, IRPs）是維持細胞鐵恆定的調控因子。已知膳食缺鐵使肝臟IRPs活性快速升高，導致鐵蛋白與粒線體酵素aconitase(m-Acon)減少。本實驗乃對缺鐵貧血大鼠施予一系列膳食鐵補充，以觀察貧血改善過程，肝臟IRPs自發活性、鐵蛋白與m-Acon含量的變化及其與血紅素濃度的關係。採用24隻Wistar品系離乳雄鼠為實驗動物，其中4隻係對照組，全程餵予鐵正常飼料；其餘先餵予缺鐵飼料約二週，使血紅素值低於60 g/L後，隨機分為四組：6R、12R、18R、36R，分別餵予添加鐵量6、12、18及35 mg/kg的含鐵飼料二週後，犧牲並取樣進行分析。隨著飼料鐵量之增高，血紅素濃度、肝重與m-Acon量隨之升高，以6R組最低，36R組最高且與對照組相當；肝臟鐵調節蛋白質IRP1與IRP2之自發活性與IRP1總量則隨之下降，以6R組最高，36R組則與對照組相當，且與血紅素值呈顯著負相關性。膳食鐵量達大鼠需要量之36R組其各項指標均可恢復正常水準，各組的血紅素濃度與m-Acon含量的復原程度相近。隨鐵營養狀況的改變，肝臟IRPs自發活性能適當應變，並選別性調控鐵蛋白及m-Acon等標的蛋白質的表現。

關鍵字

缺鐵貧血 ； 鐵補充 ； 鐵調節蛋白 ； 鐵蛋白 ； 粒線體aconitase ； 大鼠

並列摘要

Iron regulatory proteins (IRPs) are the key regulators in cellular iron homeostasis. Dietary iron deficiency rapidly increases the spontaneous activity of IRPs and reduces hepatic content of ferritin and mitochondrial aconitase (m-Acon). We evaluated the interrelationship between hemoglobin, hepatic IRPs activity and ferritin and m-Acon content during recovery from iron deficiency anemia using a series of dietary iron supplementation in a rat model. Among 24 weanling Wistar rats, four were fed a control diet (35 mg Fe/kg diet) through out the study. The rest were rendered anemic by feeding an iron-free diet for about 2 weeks and randomly assigned into four iron repletion groups: 6R, 12R, 18R and 36R, into which iron was added at 6, 12, 18 and 35 mg per kg of diet. Rats were sacrificed for tissue sampling and analysis after two weeks of iron repletion. Ferritin and m-Acon protein content was measured by immunoblotting. IRPs and total IRP1 activity was measured using gel retardation assay with an IRE probe. As dietary iron increased, hemoglobin concentration, liver weight and m-Acon content also increased, and IRP1 and IRP2 spontaneous-activity decreased. A dose-response relationship was found in this experiment. Growth, iron status and liver enzyme parameters reached the control levels only in the 36R group. The dietary iron level required for maximal hemoglobin repletion was similar to that for the recovery of hepatic m-Acon. Spontaneous IRPs activity was negatively correlated with hemoglobin concentration, and exerted a differential regulation on the expression of hepatic ferritin and m-Acon.

並列關鍵字

iron deficiency anemia ； dietary iron repletion ； iron regulatory proteins ； ferritin ； mitochondrial aconitase ； rats