膳食诱导的肥胖小鼠肠铁摄取与释放关键分子的基因表达变化

The changes of gene expression of iron transporters for duodenal iron uptake and export in dietinduced obese mice

目的探讨高脂膳食诱导的肥胖小鼠十二指肠组织中介导Fe2＋摄取和释放的关键分子——二价金属离子转运蛋白（DMT1）和膜铁转运蛋白（Fpn1）的基因表达变化。方法C57BIM6J小鼠依随机数字表法分为正常对照（NC）组和肥胖模型（OM）组，每组6只，分别以普通饲料和高脂饲料喂养14周。肥胖建模成功后，采用Real—timePCR和Westernblot法检测小鼠十二指肠DMTI、Fpn1mRNA和蛋白表达水平。结果Real—timePCR检测结果显示，与NC组相比（将NC组mRNA表达水平定为1．00），OM组小鼠Fpn1mRNA的相对表达水平（0．58±0．11）明显降低，差异有统计学意义（t=6．71，P=0．014），而DMT1mRNA相对表达水平（0．89±0．26）差异无统计学意义（t=2．01，P=0．122）。Westernblot检测结果显示，OM组小鼠十二指肠Fpn1蛋白表达量低于NC组，OM组和NC组相对表达水平分别为0．32±0．06、0．65±0．19，差异有统计学意义（t=5．37，P=0．026），而DMTI蛋白相对表达水平在OM组和NC组分别为0．88±0．21、0．92±0．17，差异无统计学意义（t=1．84，P=0．185）。结论肥胖小鼠十二指肠Fpn1mRNA及蛋白表达水平下降，而DMT1表达水平无明显变化，提示肥胖对肠铁吸收的影响可能在于肠黏膜细胞释放Fe^2＋入血循环障碍。

Objective This study aims to determine the gene expression changes of iron transporters-divalent metal transporter 1 （DMT1） and ferroportin 1 （Fpnl） in the duodenal tissue of diet-induced obese mice. Methods C57BL/6J mice were randomly divided into normal control（NC） and obesity model（OM） group, 6 in each, and fed on conventional and high-fat diet respectively for 14 weeks by table of random number. Then the DMT1 and Fpnl mRNA contents in duodenal tissues of the animals were measured by Real-time PCR method, and the protein expression levels were analyzed by Western blot test. Results The Real-time PCR detection results showed that, compared with the NC group for which the mRNA expression level was defined as 1.0, the Fpnl mRNA expression in OM group （ 0. 58 ± 0. 11 ） was reduced significantly（t = 6. 71, P = 0. 014）, whereas the relative expression level of DMT1 mRNA in OM group（0. 89±0. 26） showed no obvious alteration（t =2. 01, P =0. 122）. Western blot results showed that the relative protein expression levels of Fpnl in OM and NC group were 0. 32 ±0. 06 and 0. 65 ±0. 19, respectively, and the difference was statistically significant （ t = 5.37, P = 0. 026 ）. The DMT1 protein relative abundance was 0.88 ±0. 21 in OM group and 0.92±0.17 in NC group, and the difference has no statistical significance （t = 1.84, P = 0. 185 ）. Conclusion Fpnl gene expression is inhibited in the duodenum of diet-induced obesity mouse while DMT1 expression keeps unchanged, and this implies that decreased iron export from enterocytes into circulation might he responsible for the impaired iron absorption in obesity.