CAJ | 학술논문

目的观察外源性磷酸肌酸钠(Phosphocreatine,PCr)对大鼠脑缺血-再灌注损伤的保护作用及其作用机制.方法 Wistar雄性大鼠36只,随机(随机数字法)分为三组(n=12):假手术组(Sham组)、缺血-再灌注组(I/R组)、PCr预处理组(PCr组).采用Pulsinelli四血管法建立大鼠脑缺血-再灌注损伤模型,I/R组电凝双侧椎动脉,暴露并夹闭双侧颈总动脉,10 min后开放;PCr组在双侧颈总动脉夹闭前60 min尾静脉缓慢注射PCr 150 mg·kg-1,I/R组夹闭前60 min输注等容量生理盐水;Sham组仅穿线不夹闭.再灌注48 h后处死大鼠,TUNEL法检测大脑皮质区细胞凋亡,计算凋亡指数;测定大脑皮质区钙调蛋白(calmodulin,CaM)的活性和丙二醛(malondiadehyde,MDA)含量变化;光镜下观察大脑皮质区病理形态学变化.结果与Sham组比较,PCr组和I/R组皮质区病理损伤明显,凋亡细胞增多,CaM活性显著增强,MDA含量明显升高(P＜0.01);与I/R组比较,PCr组皮质区病理损伤明显减轻,凋亡细胞数减少,CaM活性及MDA含量显著降低(P＜0.01).结论 PCr预处理能显著减轻脑缺血-再灌注损伤,减少皮质区神经元凋亡,其机制可能与它减轻钙平衡紊乱和氧自由基代谢异常有关.
목적 관찰외원성린산기산납(Phosphocreatine,PCr)대대서뇌결혈-재관주손상적보호작용급기작용궤제.방법 Wistar웅성대서36지,수궤(수궤수자법)분위삼조(n=12):가수술조(Sham조)、결혈-재관주조(I/R조)、PCr예처리조(PCr조).채용Pulsinelli사혈관법건립대서뇌결혈-재관주손상모형,I/R조전응쌍측추동맥,폭로병협폐쌍측경총동맥,10 min후개방;PCr조재쌍측경총동맥협폐전60 min미정맥완만주사PCr 150 mg·kg-1,I/R조협폐전60 min수주등용량생리염수;Sham조부천선불협폐.재관주48 h후처사대서,TUNEL법검측대뇌피질구세포조망,계산조망지수;측정대뇌피질구개조단백(calmodulin,CaM)적활성화병이철(malondiadehyde,MDA)함량변화;광경하관찰대뇌피질구병리형태학변화.결과 여Sham조비교,PCr조화I/R조피질구병리손상명현,조망세포증다,CaM활성현저증강,MDA함량명현승고(P＜0.01);여I/R조비교,PCr조피질구병리손상명현감경,조망세포수감소,CaM활성급MDA함량현저강저(P＜0.01).결론 PCr예처리능현저감경뇌결혈-재관주손상,감소피질구신경원조망,기궤제가능여타감경개평형문란화양자유기대사이상유관.
Objective To observe the effects of exogenous sodium phosphocreatine (PCr) on cerebral repeffusion injury of rats after ischemia in order to explore the potential mechanism. Method Thirty-six healthy adult male Wistar rats with body weight 200- 220 g were randomly (random number) divided into sham operation group, ischemic reperfusion (I/R) group and PCr treatment group. The I/R model was established by using electro-cauterizing bilateral vertebral arteries and occluding bilateral common carotid arteries with atraumatic carotid clasps for 10 min, and then the clasps were released for 48 hours reperfusion. In sham operation group, bilateral common carotid arteries were exposed without occlusion. In PCr treatnent group, PCr in dose of 150 mg/kg was administered intravenously 60 min before the occlusion of bilateral common carotid arteries. Normal saline was administered intravenously instead of PCr into rats of I/R group. After reporfusion for 48 hours, the rats were sacrificed and brains removed for detections of neuron apoptosis by using TUNEL, malondialdebyde (MDA) level by using chromtometry and calmodulin (CaM) activity by using ELISA. Results Compared with sham operation group, TUNEL-positive cells, MDA level and CaM activity increased in I/R group and PGr treatment group ( P ＜0.01). Compared with I/R group, TUNEL-positive cells, MDA level and CaM activity were lower significantly in PCr treatment group ( P ＜ 0.01). Conclusions PCr can lessen cerebral ischemic reperfusion injury and neuron apoptosis, the mechanism maybe relates to the attenuation of abnormalities in calcium balance and reduction of oxygen free radicals by PCr.