肾综合征出血热患者血浆外泌体固有免疫相关长链非编码RNA含量测定及临床意义

Alterations and clinical signifecance of exosome-containing innate immunity related lncRNAs in patients of hemorrhagic fever with renal syndrome

目的观察肾综合征出血热(HFRS)患者血浆外泌体(exosome)固有免疫相关长链非编码RNA(lncRNA)的含量变化情况及其与疾病发生发展的关系。方法提取并鉴定HFRS患者及健康对照者血浆外泌体,对其中的lncRNA进行高通量测序,找出具有足够丰度的固有免疫相关lncRNA,进行实时定量PCR鉴定,分析其与HFRS发生发展的关系。结果提取血浆外泌体;发现固有免疫相关lncRNA抗病毒应答负性调节因子(NRAV)、干扰素应答负性调节因子(NRIR)及核旁斑装配转录物1(NEAT1)在HFRS患者血浆外泌体中有一定丰度,其中NEAT1含量显著低于健康对照,但与疾病的进展无明显关系。结论HFRS患者血浆外泌体中含有多种固有免疫相关lncRNA,其中NEAT1含量降低与HFRS的发生显著相关。

Objective To observe the alterations of innate immunity related long non-coding RNAs（lncRNAs） in exosomes extracted from the plasma of hemorrhagic fever with renal syndrome（HFRS） patients,and analyze their relationship with the disease stage and severity.Methods Exosomes were extracted from the plasma samples of HFRS patients,healthy controls and recovered HFRS patients.Transmission electronic microscopy and Western blotting were performed to confirm the efficiency of the extraction.lncRNA profiles in the different groups were determined by high-throughput sequencing.The contents of several innate immunity related lncRNAs were detected by quantitative real-time PCR,and their relationship with the disease stage and severity was analyzed.Results Exosomes from the plasma were accurately extracted.Innate immunity related lncRNA nuclear paraspeckle assembly transcript 1（NEAT1）,negative regulator of interferon response（NRIR）,negative regulator of antiviral response（NRAV） were found in exosomes.NEAT1 content was significantly reduced in the exosomes from HFRS patients compared with healthy controls and it was significantly restored in recovered HFRS patients.The exosome NEAT1 content was correlated with the epidemic of HFRS but had no relationship with the stage and severity of the disease.Conclusion Several innate immunity related lncRNAs exist in the exosome from HFRS patients,among which NEAT1 content significantly decreases in HFRS patients compared with healthy controls and recovered HFRS patients.The reduced NEAT1 level is correlated with the epidemic of HFRS.