脑缺血-再灌注损伤大鼠皮质微小核糖核酸表达谱的变化

Changes of microRNA expression profiling in rat cerebral cortex during cerebral ischemia-reperfusion injury

目的探讨脑缺血-再灌注损伤大鼠脑皮质微小核糖核酸(miRNAs)表达谱的变化情况。方法取雄性SD大鼠12只,采用随机分组的方法将其分为脑缺血-再灌注(IR)组和假手术组,每组6只。采用线栓法建立大鼠大脑中动脉阻塞模型,缺血1.5 h,再灌注24 h。采用基因芯片分析技术观察IR后大鼠脑皮质中miRNAs表达谱的变化。利用生物信息学软件Targetscan及miRanda,预测与IR损伤相关的差异表达miRNAs的靶基因。结果①与假手术组比较,IR组大鼠脑皮质中有36个miRNAs异常表达>1.5倍(P<0.05)。其中9个miRNAs表达上调,包括rno-miR-27a、-32*、-99b*、-129、-129-2*、-153*、-207、-326和-494;27个miRNAs表达下调,包括rno-miR-195、-190、-146b、-20a、-301a、-434*、-411、-384-5p、-140、-191、-148b-3p、-9*、-23b、-320、-140*、-151、-106b、-29a*、-872、-434、-130a、-93、-487b、-185、-652、-382、-541。②Targetscan和miRanda预测数据库均有的与IR损伤相关的靶基因为:肿瘤坏死因子α诱导蛋白1(TNFAIP1)、肿瘤坏死因子受体超家族成员1A(TNFRSF1A)、补体C1q肿瘤坏死因子相关蛋白6(C1QTNF6)、白细胞介素10(IL-10)、白细胞介素6信号转导因子(IL6ST)、血小板源性生长因子β受体(PDGFRB)、水通道蛋白11(AQP11)、热休克蛋白90αA1(HSP90αA1)及Bcl-2。结论 IR后大鼠脑皮质中miRNAs表达谱有明显变化。

Objective To investigate the changes of microRNA （miRNA） expression profiling in rat cerebral cortex during cerebral ischemia-reperfusion injury. Methods Twelve male SD rats were recrui- ted. They were randomly allocated into either an ischemia-reperfusion group or a sham operation group using a completely randomized method （n = 6 in each group）. A rat model of middle cerebral artery occlu-sion was induced by the intraluminal suture method with cerebral ischemia for 1.5 hours and reperfnsion for 24 hours. The changes of miRNA expression profiling in rat cortex after cerebral isehemia-reperfusion was observed by using microarray analysis technology. The cerebral ischemia-reperfusion injury related target genes of differential expression miRNAs were predicted using the bioinformatics software （ Targetscan and miRanda）. Results ①Compared to the sham operation group, 36 abnormal expressions were more than 1.5 times in the rat cortex of the ischemia-reperfusion group （P 〈 0.05）. The miRNA expressions in 9 of them were up-regulated, including rno-miR-27a, -32^＊ , -99b^＊ , -129, -129-2^＊ , -153^＊ , -207, -326, and -494 ; 27 miRNA expressions were down-regulated, including rno-miR -195, -190, -146b, -20a,-301a, 434^＊, 411, -384-5p, -140, -191, -148b-3p, -9^＊, -23b,- 320, -140^＊, -151, -106b, -29a^＊, -872, -434, -130a, -93, 487b, -185, -652, -382, and -541. ②Both Targetscan and Miranday prediction data-bases had the target base related to cerebral ischemia-eperfusion injury because of tumor necrosis factor alpha-induced protein 1 （TNFAIP1）, tumor necrosis factor receptor superfamily member 1A （ TNFRSF1 A）, complement-cl q tumor necrosis factor-related protein 6 （C1QTNF6）, interleukin 10 （IL-10）, interleukin 6 signal transducer （IL6ST）, platelet-derived growth factor receptor β （PDGFRB）, aquaporin 11 （ AQP11 ）, heat shock protein 90αA1 （ HSP90αA1 ）, and Bcl-2. Conclusion The microRNA expres-sion profile in rat cortex changed significantly after cerebral ischemia-reperfusion.