慢性间歇性低氧暴露对大鼠肝脏铁代谢的影响及机制研究  

The Effect of Exposure to Chronic Intermittent Hypoxia on Hepatic Iron Metabolism in Rats

作　　者：宋纪显 陈琦 贾翠玲 李博良 张智 赵亚硕[1] SONG Jixian;CHEN Qi;JIA Cuiling(Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine/Hebei University of Traditional Chinese Medicine,Hebei Shijiazhuang 050200,China)

机构地区：[1]河北省中医药结合氢医学技术创新中心/河北中医学院,河北石家庄050200

出　　处：《河北医学》2023年第7期1057-1061,共5页Hebei Medicine

基　　金：国家自然科学基金青年项目,(编号:82004127);河北省中医药管理局项目,(编号:2023354);河北省高层次人才资助项目,(编号:A202101063)。

摘　　要：目的:通过建立慢性间歇性低氧(CIH)大鼠模型,探讨CIH暴露对肝脏铁代谢的影响及可能的机制。方法:将20只SD大鼠随机分为常氧对照组(对照组)和模型组(CIH组),将模型组大鼠置于动物间歇性低氧舱内,前1.5min向舱内充入100%氮气使氧气浓度降至5%,后1.5min充入100%氧气使氧气浓度升至21%,每一循环3min,8h/d,35d;常氧对照组大鼠置于相同舱内,充入正常空气。HE染色观察肝脏损伤情况,比色法检测血清铁和总铁结合力(TIBC);普鲁士蓝染色观察肝脏铁含量;Western blot检测肝脏二价金属转运蛋白[DMT1(+ire)、DMT1(-ire)]、膜铁转运蛋白(FPN1)、转铁蛋白受体1(TfR1)、铁蛋白(FTL)、p-STAT3、STAT3蛋白表达;Q-PCR检测肝脏铁调素(hepcidin)、DMT1(+ire)、DMT1(-ire)、FPN1、TfR1、白细胞介素-6(IL-6)mRNA表达。结果:与对照组相比,模型组大鼠肝脏细胞结构紊乱,出现脂肪空泡、细胞核萎缩;与对照组相比,模型组大鼠TfR1和DMT1(+ire)mRNA及蛋白表达显著上升(P<0.05),FPN1蛋白表达明显下降(P<0.05);与对照组相比,模型组大鼠铁沉积显著增多,血清铁含量和转铁蛋白饱和度显著下降(P<0.01),FTL蛋白表达升高(P<0.05);与对照组相比,模型组大鼠肝脏中hepcidin及IL-6 mRNA表达升高(P<0.05),p-STAT3/STAT3蛋白表达比值升高(P<0.05)。结论:CIH暴露可能通过IL-6/STAT3通路调控hepcidin-FPN1系统造成肝脏中的铁沉积。Objective:To establish a rat model of chronic intermittent hypoxia(CIH)to explore the effect of CIH exposure on hepatic iron metabolism and the specific mechanism.Methods:The CIH rat model was established(the rats were placed in the animal intermittent hypoxia chamber,and the O 2 concentration was reduced to 5%by 100%N 2 in the first 1.5 min,and the O 2 concentration was increased to 21%by 100%O 2 in the last 1.5 min.Each cycle lasted for 3min,8h/d,35d).The normoxia control group rats were placed in the same chamber filled with normal air).HE staining was used to observe liver injury.Serum iron and total iron binding capacity(TIBC)were detected by colorimetric method.Iron content in liver was observed by Perls’staining.The protein expressions of divalent metal-ion transporter-1[(DMT1(+ire),DMT1(-ire)],Ferroportin 1(FPN1),transferrin receptor 1(TfR1),ferritin light chain(FTL),phosphorylation signal transduction and activator of transcription-3(p-STAT3)and signal transduction and activator of transcription-3(STAT3)in liver were detected by Western blot.The mRNA expressions of hepcidin,DMT1(+ire),DMT1(-ire),FPN1,TfR1 and interleukin 6(IL-6)in liver were detected by Q-PCR.Results:Compared with the control group,the structure of liver cells in CIH group was disordered,with fat vacuoles and nuclear atrophy.Compared with the control group,the mRNA and protein expressions of TfR1 and DMT1(+ire)in CIH group were significantly increased(P<0.05),and protein expressions of membrane FPN1 were significantly decreased(P<0.05).Compared with the control group,the iron deposition in CIH group was significantly increased,the serum iron content and transferrin saturation were significantly decreased(P<0.01),and the expression of FTL protein was significantly increased(P<0.05).Compared with the control group,the mRNA expression of hepcidin and IL-6 in the liver of rats in CIH group was significantly increased(P<0.05),and the ratio of p-STAT3/STAT3 was increased(P<0.05).Conclusion:CIH exposure may regulate hepcidin-FPN1 system by af

关 键 词：慢性间歇性低氧 铁 铁调素 肝脏 白细胞介素-6 

分 类 号：R766[医药卫生—耳鼻咽喉科] R575[医药卫生—临床医学]