CAJ | 학술논문

目的探讨酸敏感离子通道1a(ASIC1a)在大鼠全脑缺血再灌注损伤中的作用.方法成年雄性SD大鼠40只,体重250～ 300 g,采用随机数字表法,将大鼠随机分为4组(n=10):假手术组(S组)、全脑缺血再灌注组(I/R组)、ASIC1a特异性阻断剂PcTX1组(P组)和溶剂对照组(SC组).采用改良的Pulsinelli四血管阻断法制备大鼠全脑缺血再灌注损伤模型.P组和SC组于再灌注即刻分别经侧脑室注射PcTX1 (500 ng/ml)6μl和双蒸水6μl.再灌注24h时处死大鼠,取海马组织,采用Western blot法测定Caspase-3的表达,采用免疫组织化学法检测海马CA1区Bcl-2、Bax的表达水平,并观察海马病理学结果.结果与S组比较,I/R组、P组和SC组海马Caspase-3、Bcl-2和Bax表达上调(P＜0.05)；与I/R组比较,P组海马Caspase-3和Bax表达下调,Bcl-2表达上调(P＜0.05),SC组差异无统计学意义(P＞0.05).P组海马病理学损伤较I/R组减轻.结论 ASIC1a激活后可能通过上调脑组织Caspase-3和Bax的表达,下调Bcl-2的表达,诱发细胞凋亡,从而导致大鼠全脑缺血再灌注损伤.
목적 탐토산민감리자통도1a(ASIC1a)재대서전뇌결혈재관주손상중적작용.방법성년웅성SD대서40지,체중250～ 300 g,채용수궤수자표법,장대서수궤분위4조(n=10):가수술조(S조)、전뇌결혈재관주조(I/R조)、ASIC1a특이성조단제PcTX1조(P조)화용제대조조(SC조).채용개량적Pulsinelli사혈관조단법제비대서전뇌결혈재관주손상모형.P조화SC조우재관주즉각분별경측뇌실주사PcTX1 (500 ng/ml)6μl화쌍증수6μl.재관주24h시처사대서,취해마조직,채용Western blot법측정Caspase-3적표체,채용면역조직화학법검측해마CA1구Bcl-2、Bax적표체수평,병관찰해마병이학결과.결과 여S조비교,I/R조、P조화SC조해마Caspase-3、Bcl-2화Bax표체상조(P＜0.05)；여I/R조비교,P조해마Caspase-3화Bax표체하조,Bcl-2표체상조(P＜0.05),SC조차이무통계학의의(P＞0.05).P조해마병이학손상교I/R조감경.결론 ASIC1a격활후가능통과상조뇌조직Caspase-3화Bax적표체,하조Bcl-2적표체,유발세포조망,종이도치대서전뇌결혈재관주손상.
Objective To investigate the role of acid-sensing ion channel 1a(ASIC1a) in global cerebral ischemia-reperfusion injury in rats.Methods Forty male SD rats weighing 250-300 g were randomly divided into 4 groups (n =10 each): sham operation group (group S),cerebral ischemia-reperfusion group (group I/R),solvent control group (group SC) and group PcTX1 (a ASIC1 a blocker,group P).Global cerebral ischemia-reperfusion was induced by four-vessel occlusion.PcTX1(500 ng/ml)6 μl or solvent 6 μl was injected into the crerbral ventricular at the begining of reperfusion in groups P and SC respectively.The rats were sacrificed at 24 h of reperfusion,and then the hippocampi were removed for determination of Caspase-3,Bcl-2 and Bax protein expression and microscopic examination.Results Compared with group S,the expression of Caspase-3,Bcl-2 and Bax protein was up-regulated in groups I/R,SC and P (P ＜ 0.05).Compared with group I/R,the expression of Caspase-3 and Bax was down-regulated,and the expression of Bcl-2 was up-regulated in group P ( P ＜ 0.05).There was no significant difference in Caspase-3,Bcl-2 and Bax protein expression between groups I/R and SC (P ＞ 0.05).The histopathologic damage was ameliorated in group P as compared with group I/R.Conclusion ASIC1a can induce global cerebral ischemia-reperfusion injury in rats by up-regulating Caspase-3 and Bax expression,and down-regulating Bcl-2 expression and inducing apoptosis.