敲减lncRNA Gas5减轻小鼠脑外伤继发性脑水肿及神经元损伤  

Knockdown of lncRNA Gas5 suppresses secondary cerebral edema and neuron injury in mice with traumatic brain injury

作　　者：陈旭 张永安 余斌 占剑 Chen Xu;Zhang Yongan;Yu Bin;Zhan Jian(Department of Neurological Surgery,Shangrao People’s Hospital,Shangrao 334000)

机构地区：[1]上饶市人民医院神经外科

出　　处：《中国组织化学与细胞化学杂志》2019年第4期331-338,共8页Chinese Journal of Histochemistry and Cytochemistry

基　　金：江西省卫生计生委科技计划(20171557)

摘　　要：目的探讨长链非编码RNA生长停滞特异性转录本5(long non-coding RNA growth arrest speci fic transcript 5,lncRNA Gas5)在创伤性脑损伤(traumatic brain injury,TBI)小鼠模型中继发的脑水肿及神经元损伤中的作用。方法应用自由落体打击法制作小鼠TBI模型,脑内注射shRNA靶向lncRNA Gas5的腺病毒(AAV-sh-GAS5)用来敲减lncRNA Gas5,RT-qPCR检测脑组织中lncRNA Gas5的表达水平,功能性MRI成像评估脑区域的表观弥散系数(apparent dispersion coefficient,ADC)和脑血流量(cerebral blood flow,CBF),TUNEL法测定脑组织TUNEL阳性细胞数,免疫组织化学法检测脑组织中Cleaved caspase-3阳性细胞数,Western blot法检测脑组织中Bax和Cyt c水平。结果TBI后,小鼠脑组织中lncRNA Gas5表达水平随着时间递增。在TBI后24h,敲减脑lncRNA Gas5能抑制TBI诱导的脑组织中TUNEL阳性细胞数和Cleaved caspase-3阳性细胞数增加,缓解ADC值和CBF值增高,抑制TBI导致的Bax转位和Cyt c释放。结论敲减脑lncRNA Gas5对TBI小鼠有明显的神经保护作用,lncRNA Gas5可以作为治疗TBI后脑水肿及神经元损伤的一个潜在治疗靶点。Objective To investigate the effect of knockdown of long-chain non-coding RNA growth arrest speci fic transcript 5(lncRNA Gas5)on secondary brain edema and neuronal damage in a mouse model of traumatic brain injury(TBI).Methods TBI mouse model was established by using weight-drop method.Intracerebral injection of adenovirus with shRNA targeting lncRNA Gas5(AAV-sh-GAS5)was used to knockdown lncRNA Gas5.The expression level of lncRNA Gas5 in brain tissues was detected by RT-qP-CR.The apparent diffusion coefficient(ADC)and cerebral blood flow(CBF)values in brain regions were evaluated by functional MRI imaging.The number of TUNEL positive cells in brain tissues was detected by TUNEL assay.The number of Cleaved caspase-3 positive cells in brain tissues was detected by immunohistochemical staining.The expression levels of Bax and Cyt c in brain tissues were detected by Western blot.Results After TBI,the expression level of lncRNA Gas5 in mouse brain tissues increased with the course of time.At 24h after TBI,knockdown of brain lncRNA Gas5 inhibited the increase of TUNEL positive cell number and Cleaved caspase-3 positive cell number in brain tissues induced by TBI,alleviated the increase of ADC and CBF,and suppressed the release of Bax translocation and Cyt c caused by TBI.Conclusions Knockdown of brain lncRNA Gas5 has signi ficant neuroprotective effects on TBI mice,and lncRNAGas5 can be used as a potential therapeutic target for the treatment of brain edema and neuronal damage after TBI.

关 键 词：lncRNA Gas5 创伤性脑损伤 脑水肿 神经元损伤 

分 类 号：R641[医药卫生—外科学]