AIM:To explore the expression level of tristetraprolin(TTP)in rats after subarachnoid hemor-rhage(SAH)as well as the potential role of TTP in the early brain injury(EBI)after SAH in rats.METHODS:In the first experiment setting,total 56 adult male SD rats were randomly divided into sham group and SAH group.The SAH mod-el was performed by endovascular perforation.The brain tissues were taken out after SAH at 5 different time points(0,12, 24,48,72 h and 1 week).The expression of TTP in the brain tissues was detected by Western blot.In the second experi-ment,a total of 60 SD rats were divided into 4 groups: sham group, SAH group, SAH +vector group and SAH +TPP group.Neurological score,brain water content and blood-brain barrier were evaluated at 48 h after SAH.TUNEL staining was performed to detect cell apoptosis in the rat brain tissue.ELISA method was used for quantitative detection of interleu-kin-6(IL-6)and tumor necrosis factor-α(TNF-α).The protein levels of TTP,Bax,Bcl-2 and cleaved caspase-3 in the rat brain tissue were detected by Western blot.RESULTS:The protein expression of TTP in the brain was downregulated markedly from 12 h after SAH,reached the lowest level at 48 h,and then had an upward trend.After modeling for 48 h, Garcia neurological score was significantly reduced,and brain water content and Evans blue(EB)content of the brain tis-sue of the rats in SAH group were significantly higher than those in sham group(P<0.05).SAH induced significant in-creases in IL-6 and TNF-αlevels in the brain tissue(P<0.05).The number of TUNEL-stained cells was increased in the subcortical brain region after SAH compared with sham group.In addition,a lower level of Bcl-2 and higher levels of Bax and cleaved caspase-3 in the rat brains were observed at 48 h after SAH.However,the neurological deficit score was signif-icantly increased,and the brain water content and EB content in the rat brains were significantly reduced in SAH +TTP group in comparison with SAH +vector group(P<0.05).Over-expression of TTP dramatically suppressed the levels of IL-6 and TNF-αin the rat brains,and reduced the number of TUNEL positive cells.Furthermore,upregulation of TTP signifi-cantly decreased the levels of cleaved caspase-3 and Bax, and evidently enhanced the expression of Bcl-2(P<0.01). CONCLUSION:The expression of TTP is significantly decreased in early period after SAH, and enhancing the level of TTP effectively inhibits EBI following SAH in rats.%目的:分析tristetraprolin(TTP)在大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后的相对表达水平,以及TTP对SAH后早期脑损伤(early brain injury,EBI)的作用及其可能机制.方法:将56只成年雄性SD大鼠按照随机数字表法分为假手术组(sham组)和SAH组,采用血管内穿刺法建立SAH模型,SAH组分别于出血后0、12、24、48、72 h和1周取脑组织,Western blot法检测TTP在不同组别中的表达;另取60只成年雄性SD大鼠,随机分成sham组、SAH组、SAH+对照质粒(vector)组和SAH+TTP组,SAH造模48 h后检测神经功能损伤和脑组织含水率;检测脑组织内伊文思蓝(Evans blue,EB)含量以评估血脑屏障通透性;TUNEL法检测大脑皮层细胞凋亡;ELISA法检测脑组织中白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的表达;Western blot法检测脑组织中TTP、Bax、Bcl-2和cleaved caspase-3的水平.结果:与sham组比较,TTP在SAH后12 h开始表达下调,在48 h时表达最低,随后呈上升趋势;SAH组大鼠Garcia神经功能评分较sham组明显降低,脑组织含水率和EB含量较sham组均明显升高(P<0.01),脑组织中IL-6和TNF-α的表达上调(P<0.05);SAH组大鼠脑出血后细胞凋亡率显著上升(P<0.01),Bax和cleaved caspase-3的表达升高(P<0.01),而Bcl-2的表达下调(P<0.01);与SAH+vector组比较,SAH+TTP组大鼠Garcia神经功能评分明显升高,脑组织含水率和EB含量均明显降低(P<0.05),IL-6和TNF-α在脑组织中的表达下调(P<0.05),细胞凋亡率显著下调(P<0.01),Bax和cleaved caspase-3的表达下调(P<0.01),而Bcl-2的表达上调(P<0.01).结论:大鼠SAH后早期TTP表达下调,并通过其促凋亡机制参与EBI发生;上调TTP可显著减轻大鼠SAH后EBI.
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