褪黑素通过沉默信息调节因子1减轻线粒体氧化应激对脑缺血-再灌注小鼠的作用
发布时间：2018-10-21 12:34
【摘要】：目的探讨褪黑素通过沉默信息调节因子1(SIRT1)减轻线粒体氧化应激机制对脑缺血-再灌注(IR)小鼠的作用。方法通过线栓法建立小鼠短暂性大脑中动脉阻塞(MCAO)IR模型,对190只小鼠经腹腔注射褪黑素和侧脑室注射SIRT1抑制剂EX527,剔除死亡小鼠30只,按随机数字表法分为IR组、褪黑素组、褪黑素+EX527组、EX527组各40只,通过2,3,5-氯化三苯基四氮唑(TTC)法测定脑梗死体积、干湿比重法测定脑水肿并进行神经功能缺损评分。通过Western blot检测线粒体和胞质SIRT1、Ac-P53、Ac-核因子κB(Ac-NF-κB)、BCL2、BAX蛋白以及细胞色素C蛋白表达。多组间比较采用单因素方差分析。结果 (1)4组间脑梗死体积、神经功能障碍评分和脑水肿的差异均有统计学意义(F值分别为16.452、23.622和18.786,均P0.05)。4组SITR1、Ac-P53、Ac-NF-κB、BCL2、BAX表达差异均有统计学意义(F值分别为2 348.158、1 434.841、7 042.563、14 627.128和691.475,均P0.05)。4组小鼠线粒体膜电位、线粒体活性氧和复合体Ⅰ活性差异有统计学意义(F值分别为28.454、33.728和29.716,均P0.05)。(2)与IR组相比,褪黑素组的脑梗死体积缩小(32±5)mm~3比(57±5)mm~3,P0.05);神经功能障碍评分降低(2.4±0.3比3.5±0.3,P0.05);脑水肿减轻(80.2±0.9)%比(83.9±1.2)%,P0.05);SIRT1和抗凋亡蛋白BCL2的表达增加(P0.05);促凋亡蛋白BAX和Ac-P53、Ac-NF-κB的表达减少(P0.05);线粒体膜电位、线粒体复合体Ⅰ活性和细胞色素C水平提高(P0.05);胞质活性氧产物和细胞色素C水平降低(P0.05)。(3)与褪黑素组相比,褪黑素+EX527组的脑梗死体积增大[(42±5)mm~3比(32±5)mm~3,P0.05];神经功能障碍评分增高(3.2±0.3比2.4±0.3,P0.05);脑水肿加重[(83.4±0.8)%比(80.2±0.9)%,P0.05];SIRT1和抗凋亡蛋白BCL2的表达减少(P0.05);促凋亡蛋白BAX和Ac-P53、Ac-NF-κB的表达增加(P0.05);线粒体膜电位、线粒体复合体Ⅰ活性和细胞色素C水平降低(P0.05);胞质活性氧产物和胞质细胞色素C水平提高(P0.05)。结论在缺血性卒中模型小鼠中,褪黑素通过激活SIRT1信号通路,减轻线粒体氧化应激损伤和细胞死亡,从而发挥脑保护作用。
[Abstract]:Objective to investigate the protective effect of melatonin on cerebral ischemia-reperfusion (IR) mice by silencing information regulatory factor 1 (SIRT1). Methods the (MCAO) IR model of transient middle cerebral artery occlusion in mice was established by the method of thread occlusion. Thirty dead mice were killed by intraperitoneal injection of melatonin and injection of SIRT1 inhibitor EX527,. According to the method of random number table, they were divided into IR group and melatonin group. The volume of cerebral infarction was measured by (TTC) method in melatonin EX527 group and 40 rats in EX527 group. Brain edema was measured by dry-wet specific gravity method and neurological impairment score was evaluated. The expression of SIRT1,Ac-P53,Ac- nuclear factor 魏 B (Ac-NF- 魏 B), BCL2,BAX protein and cytochrome C protein) in mitochondria and cytoplasm was detected by Western blot. Single factor analysis of variance (ANOVA) was used for multi-group comparison. Results (1) the volume of diencephalic infarction in 4 groups, There were significant differences in neurological dysfunction score and cerebral edema (F = 16.452, 23.622 and 18.786, respectively, P0.05). There were significant differences in the expression of BCL2BAX in SITR1,Ac-P53,Ac-NF- 魏 B, BCL2BAX in 4 groups (F = 2 348.158 1 434.841 7 042.56314 627.128 and 691.475, respectively, P0.05). The activity of reactive oxygen species (Ros) and complex 鈪，
本文编号：2285104
[Abstract]:Objective to investigate the protective effect of melatonin on cerebral ischemia-reperfusion (IR) mice by silencing information regulatory factor 1 (SIRT1). Methods the (MCAO) IR model of transient middle cerebral artery occlusion in mice was established by the method of thread occlusion. Thirty dead mice were killed by intraperitoneal injection of melatonin and injection of SIRT1 inhibitor EX527,. According to the method of random number table, they were divided into IR group and melatonin group. The volume of cerebral infarction was measured by (TTC) method in melatonin EX527 group and 40 rats in EX527 group. Brain edema was measured by dry-wet specific gravity method and neurological impairment score was evaluated. The expression of SIRT1,Ac-P53,Ac- nuclear factor 魏 B (Ac-NF- 魏 B), BCL2,BAX protein and cytochrome C protein) in mitochondria and cytoplasm was detected by Western blot. Single factor analysis of variance (ANOVA) was used for multi-group comparison. Results (1) the volume of diencephalic infarction in 4 groups, There were significant differences in neurological dysfunction score and cerebral edema (F = 16.452, 23.622 and 18.786, respectively, P0.05). There were significant differences in the expression of BCL2BAX in SITR1,Ac-P53,Ac-NF- 魏 B, BCL2BAX in 4 groups (F = 2 348.158 1 434.841 7 042.56314 627.128 and 691.475, respectively, P0.05). The activity of reactive oxygen species (Ros) and complex 鈪，
本文编号：2285104
本文链接：https://www.wllwen.com/yixuelunwen/shenjingyixue/2285104.html
最近更新
教材专著
