CAJ | 학술논문

目的评价线粒体ATP敏感性钾通道在头部浅低温减轻大鼠全脑缺血再灌注损伤中的作用.方法健康雄性SD大鼠32只,体重200～250 g,随机分为4组(n=8):假手术组(S组)、全脑缺血再灌注组(I/R组)、头部浅低温组(H组)和5-羟基葵酸钠组(5-HD组).采用三血管阻断法建立大鼠全脑缺血再灌注模型.S组仅分离血管,不阻断;I/R组制备大鼠全脑缺血再灌注模型;H组于再灌注前即刻实施头部浅低温(使鼓膜温度在1 min内降至32～34℃),维持3 h后复温;5-HD组于缺血前30 min腹腔注射5-羟基葵酸钠10 mg/kg,于再灌注前即刻实施头部浅低温.于再灌注12 h时评估大鼠神经行为学(跨格次数和转体时间),采用EIJSA法测定血清神经元特异性烯醇化酶(NSE)的浓度,电镜下观察额叶皮质神经元的超微结构.结果与S组比较,I/R组、H组和5-HD组跨格次数减少,转体时间延长,I/R组和5-HD组血清NSE浓度升高(P<0.05),H组血清NSE浓度差异无统计学意义(P0.05);与I/R组比较,H组跨格次数增多,转体时间缩短,血清NSE浓度降低,5-HD组转体时间缩短(P<0.05),其余指标差异无统计学意义(P0.05);与H组比较,5-HD组跨格次数减少,转体时间延长,血清NSE浓度升高(P<0.05).H组额叶皮质神经元病理学改变较I/R组和5-HD组减轻,5-HD组与I/R组损伤程度相似.结论头部浅低温减轻大鼠全脑缺血再灌注损伤可能与开放线粒体ATP敏感性钾通道有关.
목적 평개선립체ATP민감성갑통도재두부천저온감경대서전뇌결혈재관주손상중적작용.방법 건강웅성SD대서32지,체중200～250 g,수궤분위4조(n=8):가수술조(S조)、전뇌결혈재관주조(I/R조)、두부천저온조(H조)화5-간기규산납조(5-HD조).채용삼혈관조단법건립대서전뇌결혈재관주모형.S조부분리혈관,불조단;I/R조제비대서전뇌결혈재관주모형;H조우재관주전즉각실시두부천저온(사고막온도재1 min내강지32～34℃),유지3 h후복온;5-HD조우결혈전30 min복강주사5-간기규산납10 mg/kg,우재관주전즉각실시두부천저온.우재관주12 h시평고대서신경행위학(과격차수화전체시간),채용EIJSA법측정혈청신경원특이성희순화매(NSE)적농도,전경하관찰액협피질신경원적초미결구.결과 여S조비교,I/R조、H조화5-HD조과격차수감소,전체시간연장,I/R조화5-HD조혈청NSE농도승고(P<0.05),H조혈청NSE농도차이무통계학의의(P0.05);여I/R조비교,H조과격차수증다,전체시간축단,혈청NSE농도강저,5-HD조전체시간축단(P<0.05),기여지표차이무통계학의의(P0.05);여H조비교,5-HD조과격차수감소,전체시간연장,혈청NSE농도승고(P<0.05).H조액협피질신경원병이학개변교I/R조화5-HD조감경,5-HD조여I/R조손상정도상사.결론 두부천저온감경대서전뇌결혈재관주손상가능여개방선립체ATP민감성갑통도유관.
Objective To investigate the role of mitochondrial ATP-sensitive potassium channel (mito-KATP) in the mild head hypothermia induced attenuation of global cerebral ischemia-reperfusion (I/R) injury. Methods Thirty-two healthy male SD rats weighing 200-250 g were randomly divided into 4 groups (n=8each): group Ⅰ sham operation (S);group Ⅱ I/R;group Ⅲ mild head hypothermia + I/R (H) and group 5-HD + mild head hypothermia + I/R (5-HD). The animals were anesthetized with intraperitoneal 10% chloral hydrate 0.35 g/kg and tracheostomized. The animals kept spontaneous breathing. Global cerebral I/R was produced by temporary occlusion of bilateral common carotid arteries and vertebro-basilar artery for 10 rain followed by reperfusion. Global cerebral I/R was verified by pale conjunctiva and increased respiratory rate. In group Ⅲ(H) and Ⅳ (5-HD) mild head hypothermia was produced by 10℃ normal saline (NS) 3-5 ml injected slowly iv and ice bag and 0℃ gauze placed around the heads. Tympanic membrane temperature was reduced to 32-34℃ within 1 min. The head cooling was started before reperfusion and maintained for 3 h. During head cooling, the body temperature was maintained at 36.5-37.5℃ (rectal). In group Ⅳ(5-HD) 5-HD 10 mg/kg was injected IP 30 min before cerebral isehemia. The open field test (OFT) and inclined plane test (IPT) were performed at 12 h of repeffusiou. Venous blood samples were taken after OFT and IPT test for determination of serum NSE concentration by ELISA. The animals were then killed and the right frontal lobes were removed for examination of the changes in the ultrastructure of neurons in cortex with electron microscope. Results The serum NSE concentration was significantly lower in group H (Ⅲ) than in group Ⅱ (I/R) and Ⅳ (5-HD). Electron microscopic examination showed that the histo-pathological changes of the neurons in the cortex were significantly slighter in group H than in group I/R and 5-HD.Conclusion Mild head hypothermia has protective effects on the brain against I/R injury. Mito-KATP plays an important role in the protective effects.