铁超载对NAFLD大鼠DMT1和FPN1基因表达影响

Effects of iron overload on gene expressions of DMT1 and FPN1 in rats with nonalcoholic fatty liver disease

目的探讨铁超载对高脂膳食诱导非酒精性脂肪肝病(NAFLD)大鼠二价金属离子转运蛋白(DMT1)、膜铁转运蛋白(FPN1)基因表达影响。方法采用高脂高铁饮食诱导非酒精性脂肪肝病大鼠模型,测定大鼠血清甘油三酯、总胆固醇、葡萄糖、胰岛素水平,计算胰岛素抵抗指数(HOMA-IR);苏木素–伊红染色观察大鼠肝脏病理组织改变;逆转录–聚合酶链反应(RT-PCR)法检测大鼠十二指肠DMT1和FPN1 m RNA表达水平。结果高脂高铁组大鼠血清TG含量[(0.61±0.07)μmol/L],明显高于对照组(P<0.05),血清胰岛素和HOMA-IR分别为[(27.73±8.29)m IU/L和(6.06±1.88)],明显高于对照组和高脂组(P<0.05);高脂高铁组大鼠肝脏脂肪变性程度较高脂组严重;高脂高铁组大鼠十二指肠DMT1和FPN1 m RNA相对表达量分别为[(0.81±0.03)和(0.69±0.11)],均低于对照组(P<0.05)。结论高脂高铁联合作用可诱发大鼠胰岛素抵抗,加重肝脏脂肪变性程度,并使大鼠肠道铁吸收负反馈调节作用降低。

Objective To investigate the effects of iron overload and high fat diet on the level of divalent metal transporter 1（DMT1） and ferroportin 1（FPN1） m RNA expressions in duodenum of rats with nonalcoholic fatty liver disease（NAFLD）. Methods High fat and high iron diet were used to construct NAFLD model in rats. Serum levels of triglycerides（TG）, total cholesterol（TC）, glucose（Glu）, and insulin（INS） of the experimental rats were detected and the index of homeostatic measurement assessment-insulin resistance（HOMA-IR） was calculated. Pathological changes in livers were observed with hematoxylin-eosin staining. The expression levels of DMT1 and FPN1 m RNA in the duodenums were measured using reverse transcription polymerase chain reaction（RT-PCR） method. Results Serum TG level of the rats with high fat and high-dose iron supplement was 0.61 ± 0.07 and significantly higher than that of the control rats（P〈0.05）.Serum insulin and HOMA-IR index of the rats with high fat and high-dose iron supplement were 27.73 ± 8.29 m IU/L and6.06 ± 1.88, and both higher than those of the control rats and the rats only with high fat diet（P〈0.05 for all）. The hepatic steatosis of the rats with high fat and high-dose iron supplement was more serious than that of the rats only with high fat.Duodenal DMT1 m RNA and FPN1 m RNA expressions in the rats with high fat and high-dose iron supplement were 0.81 ±0.03 and 0.69 ± 0.11, and both significantly lower than those of the control rats（both P〈0.05）. Conclusion High fat and high iron diet could induce insulin resistance, aggravate hepatic steatosis, and decrease the negative feedback regulation of duodenum iron absorption in rats with NAFLD.