Lnc-FOXD3-AS1通过激活SMAD1/5/8促进缺铁性贫血大鼠体内Hepcidin表达  

Lnc-FOXD3-AS1 Promotes the Expression of Ferrimodulin in Rats with Iron Deficiency Anemia by Activating SMAD1/5/8

作　　者：安媛媛·安林 籍雁敏 热西丹·阿布力海提 木尼热·买买提尼牙孜 佐日汗·艾依萨 ANYUANYUAN Anlin;JI Yanmin(The Seventh Affiliated Hospital of Xinjiang Medical University,Xinjiang Urumqi 830000,China)

机构地区：[1]新疆医科大学第七附属医院儿科,新疆乌鲁木齐830000 [2]新疆医科大学第二附属医院儿科,新疆乌鲁木齐830000

出　　处：《河北医学》2023年第12期1992-1998,共7页Hebei Medicine

基　　金：新疆少数民族科技人才特殊培养计划科研项目(编号:2020D03007)。

摘　　要：目的:探讨长链非编码RNA FOXD3-AS1(lnc-FOXD3-AS1)对缺铁性贫血(IDA)大鼠模型Hepcidin表达调控作用。方法:无特定病原级(SD大鼠)接受反复放血和饲喂低铁饲料诱导IDA模型。将大鼠分为对照组、IDA组、IDA大鼠经lnc-FOXD3-AS1过表达治疗组(pcDNA-FOXD3-AS1+IDA组)、IDA大鼠经过表达空载体治疗组(pcDNA-null+IDA组)、IDA大鼠经pcDNA-FOXD3-AS1联合Smad1/5/8的激活抑制剂Compound C治疗组(pcDNA-FOXD3-AS1+Compound C+IDA组),每组n=8。试剂盒法检测各组大鼠血液中铁含量,用qRT-PCR法检测肝脏组织和血清中lnc-FOXD3-AS1的表达,western blot和ELISA法检测大鼠肝脏组织和血清Hepcidin以及SMAD1/5/8蛋白的表达和激活。结果:IDA组的大鼠IDA模型诱导成功。与对照组比,IDA组中大鼠肝脏组织和血清中铁含量维持在缺铁状态(均P<0.05),且Hepcidin、lnc-FOXD3-AS1和SMAD1/5/8的表达水平都显著降低(均P<0.05),另外SMAD1/5/8的磷酸化水平明显降低(P<0.05)。与pcDNA-null+IDA组比,pcDNA-FOXD3-AS1+IDA组的肝脏组织和血清中铁含量明显增加(均P<0.05),且Hepcidin、lnc-FOXD3-AS1和SMAD1/5/8的表达水平都显著升高(均P<0.05),另外SMAD1/5/8的磷酸化水平明显升高(P<0.05)。与pcDNA-FOXD3-AS1+IDA组比,pcDNA-FOXD3-AS1+Compound C+IDA组的肝脏组织和血清中铁含量明显减少(均P<0.05),且Hepcidin和和SMAD1/5/8的表达水平都显著降低(均P<0.05)。结论:lnc-FOXD3-AS1在IDA大鼠体内低表达,其通过激活SMAD1/5/8信号促进IDA大鼠体内Hepcidin的表达。本研究对于更深入地理解IDA发生的生物学网络机制具有重要意义。Objective:To investigate the regulatory effect of long-chain noncoding RNA FOXD3-AS1(Lnc-FoxD3-AS1)on the expression of hepcidin in rats with iron deficiency anemia(IDA).Methods:The IDA model was induced by repeated bloodletting and feeding low iron diet to SD rats without specific pathogen grade.The rats were divided into control group,IDA group,IDA rats treated with LCN-FoxD3-AS1 overexpression group(pcDNA-FOXD3-AS1+IDA group),IDA rats treated with empty vector expression group(pcDNA-null+IDA group),and IDA rats treated with pcDNA-FOXD3-AS1 combined with Sm ad1/5/8 acti-vation inhibitor Compound C treatment group(pcDNA-FOXD3-AS1+Compound C+IDA group),n=8 for each group.The content of iron in blood of rats in each group was detected by kit method,the expression of Lnc-FOXD3-AS1 in liver tissue and serum was detected by qRT-PCR,and the expression and activation of ferrimodulin and SMAD1/5/8 protein in liver tissue and serum were detected by western blot and ELISA.Re-sults:Iron deficiency anemia model was successfully induced in IDA group.Compared with the control group,iron content in liver tissue and serum of rats in IDA group remained in the state of iron deficiency(all P<0.05),and the expression levels of ferrimodulin,LCNC-FOXD3-AS1 and SMAD1/5/8 were significantly de-creased(all P<0.05),and the phosphorylation level of SMAD1/5/8 was significantly decreased(all P<0.05).Compared with pcDNA-null+IDA group,iron content in liver tissue and serum in pcDNA-FOXD3-AS1+IDA group was significantly increased(all P<0.05),and the expression levels of ferrimodulin,LCNA-FOXD3-AS1 and SMAD1/5/8 were significantly increased(all P<0.05).Moreover,the phosphorylation lev-el of SMAD1/5/8 was significantly increased(P<0.05).Compared with pcDNA-FOXD3-AS1+IDA group,the iron content in liver tissue and serum of pcDNA-FOXD3-AS1+Compound C+IDA group was significantly decreased(all P<0.05),and the expression levels of ferromodulin and SMAD1/5/8 were significantly de-creased(all P<0.05).Conclusion:lnc-FOXD3-AS1 is downregulated in the IDA

关 键 词：长链非编码RNA FOXD3-AS1 SMAD1/5/8 缺铁性贫血大鼠模型 HEPCIDIN 

分 类 号：R556.3[医药卫生—血液循环系统疾病] R-332[医药卫生—内科学]