中国临床康复
中國臨床康複
중국림상강복
CHINESE JOURNAL OF CLINICAL REHABILITATION
2004年
16期
3174-3175
,共2页
李琴%毕明俊%张红%郑青立%郭云良
李琴%畢明俊%張紅%鄭青立%郭雲良
리금%필명준%장홍%정청립%곽운량
脑缺血/病理生理学%肌苷/治疗应用%基因表达%细胞色素C
腦缺血/病理生理學%肌苷/治療應用%基因錶達%細胞色素C
뇌결혈/병리생이학%기감/치료응용%기인표체%세포색소C
背景:细胞色素C(chromosome C,CytC)的释放是细胞凋亡的重要环节之一.肌苷对脑缺血损伤神经细胞凋亡可能具有一定的抑制作用,但其机制尚不十分清楚.目的:研究肌苷对大鼠局灶性脑缺血再灌注后神经细胞凋亡和CytC基因表达的影响.设计:随机对照的实验研究.地点和材料:本实验在青岛大学医学院脑血管病研究所和山东省脑血管病防治重点实验室完成.成年健康雌性SD大鼠68只,体质量230～280 g,清洁级,由中国科学院上海实验动物中心提供.干预:应用线栓法建立大鼠大脑中动脉阻塞再灌注模型,随机分为治疗组(腹腔注射肌苷,100mg/kg)32只和对照组(腹腔注射生理盐水)32只,每组再随机分为缺血1.5 h再灌注2,6,12,24 h,2,3,7,14 d组(n=4),另外4只作假手术组.原位末端标记和原位杂交技术分别观察神经细胞凋亡和CytC mRNA表达.主要观察指标:脑缺血再灌注后神经细胞凋亡和CytC mRNA表达.结果:脑缺血再灌注后2 h皮质区与纹状体区即出现凋亡细胞并逐渐增加,分别于1 d和2 d达高峰,之后逐渐减少,至14 d接近于假手术组水平;经肌苷治疗后凋亡神经细胞减少,其中再灌注12 h～7 d较对照组有显著性差异.CytC mRNA于脑缺血再灌注2h开始表达,皮质区12 h达高峰,纹状体区1 d达高峰,以后逐渐下降;肌苷治疗组CytC mRNA表达于再灌注12 h～7 d在皮质区、12 h～14d在纹状体区较对照组显著降低.结论:肌苷可能通过抑制细胞凋亡及相关基因表达而发挥其神经保护作用,对治疗脑血管病有潜在的应用价值.
揹景:細胞色素C(chromosome C,CytC)的釋放是細胞凋亡的重要環節之一.肌苷對腦缺血損傷神經細胞凋亡可能具有一定的抑製作用,但其機製尚不十分清楚.目的:研究肌苷對大鼠跼竈性腦缺血再灌註後神經細胞凋亡和CytC基因錶達的影響.設計:隨機對照的實驗研究.地點和材料:本實驗在青島大學醫學院腦血管病研究所和山東省腦血管病防治重點實驗室完成.成年健康雌性SD大鼠68隻,體質量230～280 g,清潔級,由中國科學院上海實驗動物中心提供.榦預:應用線栓法建立大鼠大腦中動脈阻塞再灌註模型,隨機分為治療組(腹腔註射肌苷,100mg/kg)32隻和對照組(腹腔註射生理鹽水)32隻,每組再隨機分為缺血1.5 h再灌註2,6,12,24 h,2,3,7,14 d組(n=4),另外4隻作假手術組.原位末耑標記和原位雜交技術分彆觀察神經細胞凋亡和CytC mRNA錶達.主要觀察指標:腦缺血再灌註後神經細胞凋亡和CytC mRNA錶達.結果:腦缺血再灌註後2 h皮質區與紋狀體區即齣現凋亡細胞併逐漸增加,分彆于1 d和2 d達高峰,之後逐漸減少,至14 d接近于假手術組水平;經肌苷治療後凋亡神經細胞減少,其中再灌註12 h～7 d較對照組有顯著性差異.CytC mRNA于腦缺血再灌註2h開始錶達,皮質區12 h達高峰,紋狀體區1 d達高峰,以後逐漸下降;肌苷治療組CytC mRNA錶達于再灌註12 h～7 d在皮質區、12 h～14d在紋狀體區較對照組顯著降低.結論:肌苷可能通過抑製細胞凋亡及相關基因錶達而髮揮其神經保護作用,對治療腦血管病有潛在的應用價值.
배경:세포색소C(chromosome C,CytC)적석방시세포조망적중요배절지일.기감대뇌결혈손상신경세포조망가능구유일정적억제작용,단기궤제상불십분청초.목적:연구기감대대서국조성뇌결혈재관주후신경세포조망화CytC기인표체적영향.설계:수궤대조적실험연구.지점화재료:본실험재청도대학의학원뇌혈관병연구소화산동성뇌혈관병방치중점실험실완성.성년건강자성SD대서68지,체질량230～280 g,청길급,유중국과학원상해실험동물중심제공.간예:응용선전법건립대서대뇌중동맥조새재관주모형,수궤분위치료조(복강주사기감,100mg/kg)32지화대조조(복강주사생리염수)32지,매조재수궤분위결혈1.5 h재관주2,6,12,24 h,2,3,7,14 d조(n=4),령외4지작가수술조.원위말단표기화원위잡교기술분별관찰신경세포조망화CytC mRNA표체.주요관찰지표:뇌결혈재관주후신경세포조망화CytC mRNA표체.결과:뇌결혈재관주후2 h피질구여문상체구즉출현조망세포병축점증가,분별우1 d화2 d체고봉,지후축점감소,지14 d접근우가수술조수평;경기감치료후조망신경세포감소,기중재관주12 h～7 d교대조조유현저성차이.CytC mRNA우뇌결혈재관주2h개시표체,피질구12 h체고봉,문상체구1 d체고봉,이후축점하강;기감치료조CytC mRNA표체우재관주12 h～7 d재피질구、12 h～14d재문상체구교대조조현저강저.결론:기감가능통과억제세포조망급상관기인표체이발휘기신경보호작용,대치료뇌혈관병유잠재적응용개치.
BACKGROUND: The release of cytochrome C (Cyt C) from mitochondria is a critical step in the apoptosis process. Inosine could play a certain inhibiting role in neuronal apoptosis after cerebral ischemic injury, but its mechanism is not known thoroughly.OBJECTIVE: To investigate the effects of inosine on neuronal apoptosis and expression of cytochrome C mRNA in rats after focal cerebral ischemic reperfusion.DESIGN: A randomized controlled experimental research.SETTING and MATERIALS: This experiment was carried out in the Institute of Cerebrovascular Diseases, Medical College of Qingdao University and the Key Laboratory of the Prevention and Cure of Cerebrovascular Diseases of Shandong Province. Sixty-eight adult healthy female SD rats,weighting 230 - 270 g, clearing grade, were purchased from Shanghai Experimental Animal Center of Chinese Academy of Science.INTERVENTION: The model of ischemic reperfusion in SD rats was established by middle cerebral artery occlusion with a nylon monofilament suture. The rats were randomly divided into treatment group(32 rats injected with inosine intraperisoneally, 100 mg/kg) and control group(32 rats injected with saline solution intraperisoneally). Each group was then randomly divided into eight subgroups with 4 rats in each at 2 hours, 6, 12, 24 hours,and 2, 3, 7, 14 days of reperfusion after 1.5 hours' ischemia. The other 4rats served as sham-operation group. In situ hybridization was performed to examine the expression of cytochrome C mRNA while terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-label ing(TUNEL) staining was made to characterize apoptosis.MAIN OUTCOME MEASURES: Neuronal apoptosis and expression of cytochrome C mRNA in brain tissues after cerebral ischemic reperfusion.RESULTS: TUNEL-positive cells were observed at 2 hours of reperfusion, the number increased gradually and peaked at 1 day and 2 days of reperfusion in the cortex and striatum, respectively, then reduced to the level of sham-operation group at 14 days. In inosine group, the number of TUNEL-positive cells decreased during 12 hours-7 days of reperfusion compared to that of the control group. Cytochrome C mRNA was expressed in the cortex and striatum of ischemic hemisphere as early as 2 hours of reperfusion, reached a peak at 12hours and 1 day in the cortex and striatum, respectively. Inosine treatment could diminish the cytochrome C mRNA expression at 12 hours to 7 days in the cortex and 12 hours to 14 days in the striatum, respectively.CONCLUSION: Inosine can exert a protective effect on nerves by inhibiting apoptosis and related mRNA expression. Therefore, it may be a potential compound in treating cerebrovascular diseases.
