摘要
目的观察高压氧(HBO)对永久性大脑中动脉阻塞(MCAO)大鼠凋亡诱导因子(AIF)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的影响,探讨凋亡途径。方法选取SD大鼠60只,制作大鼠永久MCAO模型,按照随机数字表法将其分为对照组和HBO组,每组30只。HBO组造模成功后3h予以HBO干预,压力0.2MPa,持续9h,于HBO干预介入后1h、3h、5h、7h、9h吸氧。对照组呼吸常压空气。MCAO造模成功后3h、13h、72h行Garcia评分,MCAO造模成功后13h、72h检测细胞凋亡情况、细胞核和线粒体AIF、Caspase-3水平。结果与组内3h比较,2组大鼠13h的Garcia评分有所改善(P<0.05),72h的Garcia评分改善更明显(P<0.05)。2组大鼠缺血半暗带区各时间点皆可见大量凋亡细胞,对照组72h凋亡细胞数少于13h,差异有统计学意义(P<0.05),与对照组比较,HBO组13h时的细胞凋亡数较少(P<0.05)。与组内13h比较,2组大鼠72h时AIF在细胞核中的表达水平均下降(P<0.05),AIF在线粒体中的表达水平均升高(P<0.05)。与对照组同时间点比较,HBO组13h[(1.10±0.08)ng/ml]、72h[(0.41±0.07)ng/ml]AIF在细胞核中的表达水平均较低(P<0.05),13h[(1.60±0.05)ng/ml]、72h[(5.94±0.14)ng/ml]AIF在线粒体中的表达水平均较高(P<0.05)。2组大鼠Caspase-3水平在13h增高(正常时胞浆内水平为0)。与组内13h比较,2组大鼠Caspase-3水平在72h下降(P<0.05)。结论HBO治疗可以改善大鼠神经功能,抑制AIF由线粒体向细胞核转位,降低Caspase-3水平,其机制可能是通过线粒体非Caspase依赖途径及Caspase途径减少细胞凋亡。
Objective To observe the effect of hyperbaric oxygenation (HBO) on apoptosis-inducing factor (AIF) and Caspase-3 levels in rats with permanent middle cerebral artery occlusion (MCAO), and to elucidate the apoptosis pathways. Methods Sixty Sprague-Dawley rats were subjected to permanent MCAO and then randomly divided into a control group and an HBO group, each of 30. Three hours later the rats of the HBO group were put into a hyperbaric cabin held at a pressure of 0.2 MPa for 9 hours. They inhaled supplementary oxygen at the 1st, 3rd, 5th, 7th and 9th hour while the rats in the control group inhaled air at normal pressure. The neurological outcome was measured at the 3rd, 13th and 72nd hour after the MCAO using Garcia scores. Apoptosis in the tissue of the ischemic penumbra, nuclear and mitochondrial AIF and Caspase-3 levels were measured at the 13th and 72nd hours after the modeling. Results The scores were significantly higher at the 13th hour than after the 3rd hour in both groups, and then even higher at the 72nd hour. Apoptosis was evident in the ischemic penumbra at the 13th and 72nd hours in both groups, but the number of cells was less at the 72nd hour than at the 13th hour in the control group. There was significantly less apoptosis in the HBO group than in the control group at the 13th hour. The average AIF level had significantly decreased in the nuclei and increased in the mitochondria by the 72nd hour compared with the 13th hour in both groups. The average levels of nuclear AIF at the 13th hour and the 72nd hour were lower than those in the mitochondria. But they were significantly higher in the HBO group than in the control group at the same time points. The levels of Caspase-3, normally zero, had increased by the 13th hour in both groups. The average level of Caspase-3 was significantly lower in both groups at the 72nd hour than at the 13th hour. Conclusions HBO can improve neurological function, inhibit the transfer of AIF from the mitochondria to the nucleus and reduce Caspase-3 levels. The mechan
作者
于秋红
刘亚玲
王丛
李婕
吉康祥
薛连璧
Yu Qiuhong;Liu Yaling;Wang Cong;Li Jie;Ji Kangxiang;Xue Lianbi(Department of Hyperbaric Oxygen,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)
出处
《中华物理医学与康复杂志》
CAS
CSCD
北大核心
2019年第8期561-564,共4页
Chinese Journal of Physical Medicine and Rehabilitation
