CAJ | 학술논문

目的探讨酸敏感离子通道(ASICs)在大鼠全脑缺血再灌注损伤中的作用.方法雄性SD大鼠48只,体重250～310 g,采用随机数字表法,将大鼠随机分为4组(n=12):假手术组(S组)、缺血再灌注组(I/R组)、生理盐水组(NS组)和ASICs阻断剂组(A组).I/R组、NS组和A组采用阻断双侧颈总动脉和基底动脉10 min的方法制备全脑缺血再灌注模型,NS组和A组于再灌注前即刻分别静脉注射生理盐水6 ml/kg和ASICs阻断剂阿米洛利0.3 mg/kg.各组取6只大鼠,分别于缺血前(基础状态)、缺血即刻及再灌注20 min期间每隔10 min收集一次海马CA1区微透析液,测定微透析液中乳酸浓度.再灌注8 h时各组取另外6只大鼠,进行方格爬行实验和斜板实验,以评价神经行为学;然后取脑组织,计算脑含水量,并在光镜及电镜下观察大脑皮质的病理学结果.结果与S组比较,I/R组和NS组微透析液中乳酸浓度和脑含水量升高,发生神经行为学障碍(P＜0.05);与I/R组比较,A组微透析液中乳酸浓度和脑含水量降低,神经行为学改善(P＜0.05),NS组上述指标差异无统计学意义(P＞0.05).A组脑组织损伤程度轻于I/R组.结论 ASICs参与了大鼠全脑缺血再灌注损伤的发生.
목적 탐토산민감리자통도(ASICs)재대서전뇌결혈재관주손상중적작용.방법 웅성SD대서48지,체중250～310 g,채용수궤수자표법,장대서수궤분위4조(n=12):가수술조(S조)、결혈재관주조(I/R조)、생리염수조(NS조)화ASICs조단제조(A조).I/R조、NS조화A조채용조단쌍측경총동맥화기저동맥10 min적방법제비전뇌결혈재관주모형,NS조화A조우재관주전즉각 분별정맥주사생리염수6 ml/kg화ASICs조단제아미락리0.3 mg/kg.각조취6지대서,분별우결혈전(기출상태)、결혈즉각급재관주20 min기간매격10 min수집일차해마CA1구미투석액,측정미투석액중유산농도.재관주8 h시각조취령외6지대서,진행방격파행실험화사판실험,이평개신경행위학;연후취뇌조직,계산뇌함수량,병재광경급전경하관찰대뇌피질적병이학결과.결과 여S조비교,I/R조화NS조미투석액중유산농도화뇌함수량승고,발생신경행위학장애(P＜0.05);여I/R조비교,A조미투석액중유산농도화뇌함수량강저,신경행위학개선(P＜0.05),NS조상술지표차이무통계학의의(P＞0.05).A조뇌조직손상정도경우I/R조.결론 ASICs삼여료대서전뇌결혈재관주손상적발생.
Objective To investigate the role of acid-sensing ion channels (ASICs) in global cerebral ischemia-reperfusion (I/R) injury in rats. Methods Forty-eight adult male Sprague-Dawley rats weighing 250-310 g were randomly divided into 4 groups ( n = 12 each): sham operation group (group S); global cerebral I/R group (group I/R); normal saline group (group NS) and specific ASIC blocker amiloride group (group A). Global cerebral I/R was produced by occlusion of 3 vessels ( 10 min occlusion of the bilateral common carotid arteries and basilar artery) followed by reperfusion. In group NS and A, NS 6 ml/kg and amiloride 0.6 mg/kg were injected through femoral vein immediately before reperfusion respectively. Six rats in each group were selected, the dialysate in CA1 area was collected before ischemia (baseline), immediately after ischemia and during 20 min reperfusion (once every 10 min) for determination of lactate concentrations. The left 6 rats in each group were elected at 8 h of reperfusion and the open field test and inclined plane test were peeformed to assess neurological behavior.The rats were then sacrificed and brain tissues taken for microscopic examination and brain water content was calculated. Results Compared with group S, the concentration of lactate in the dialysate and brain water content were significantly increased and neurological deficits developed in group I/R and NS (P ＜ 0.05). Compared with group I/R, the concentration of lactate in the dialysate and brain water content were significantly decreased and neurological deficits were improved in group A ( P ＜ 0.05 ), but no significant change in the parameters mentioned above was found in group NS ( P ＞ 0.05). Microscopic examination showed that the damage to the brain tissues was attenuated in group A compared with group I/R. Conclusion ASICs are involved in the development of global cerebral I/R injury in rats.