CAJ | 학술논문

目的探讨醋甲唑胺对自发性蛛网膜下腔出血(SAH)小鼠认知功能损害的影响及机制.方法 90只雄性C57 BL/6J小鼠随机分为假手术组、SAH组及醋甲唑胺组,用血管内刺破法建立SAH模型,激光多普勒血流仪记录出血侧脑血流量的变化.旷场试验评价小鼠的感觉运动及认知功能,原位末端转移酶标记(TUNEL)法检测出血侧海马的变性和凋亡神经元的变化,免疫组织化学法检测海马区的活化型半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3的表达.结果 SAH总死亡率为25.3％,其中SAH组26.1％,醋甲唑胺组24.4％,差异无统计学意义(P＞0.05).醋甲唑胺组3、7、14d的旷场试验运动总距离及中央格时间较SAH组改善明显(P＜0.05);在出血侧大脑半球,SAH组(87.11 ±6.73) μm及醋甲唑胺组(89.39±7.22)μm的大脑中动脉直径较假手术组的大脑中动脉直径(106.89±8.66) μm明显变小(P＜0.05),但SAH组和醋甲唑胺组大脑中动脉直径比较差异无统计学意义(P＞0.05);醋甲唑胺组出血侧海马区TUNEL阳性细胞与SAH组比较明显减少,差异有统计学意义(P＜0.05);醋甲唑胺组出血侧海马区Caspase-3阳性细胞比值与SAH组比较明显降低,差异有统计学意义(P＜0.05).结论醋甲唑胺可改善SAH小鼠的认知功能,并可能是通过抑制Caspase-3的激活、抑制海马神经元的凋亡起作用.
목적 탐토작갑서알대자발성주망막하강출혈(SAH)소서인지공능손해적영향급궤제.방법 90지웅성C57 BL/6J소서수궤분위가수술조、SAH조급작갑서알조,용혈관내자파법건립SAH모형,격광다보륵혈류의기록출혈측뇌혈류량적변화.광장시험평개소서적감각운동급인지공능,원위말단전이매표기(TUNEL)법검측출혈측해마적변성화조망신경원적변화,면역조직화학법검측해마구적활화형반광안선천동안산특이성단백매(Caspase)-3적표체.결과 SAH총사망솔위25.3％,기중SAH조26.1％,작갑서알조24.4％,차이무통계학의의(P＞0.05).작갑서알조3、7、14d적광장시험운동총거리급중앙격시간교SAH조개선명현(P＜0.05);재출혈측대뇌반구,SAH조(87.11 ±6.73) μm급작갑서알조(89.39±7.22)μm적대뇌중동맥직경교가수술조적대뇌중동맥직경(106.89±8.66) μm명현변소(P＜0.05),단SAH조화작갑서알조대뇌중동맥직경비교차이무통계학의의(P＞0.05);작갑서알조출혈측해마구TUNEL양성세포여SAH조비교명현감소,차이유통계학의의(P＜0.05);작갑서알조출혈측해마구Caspase-3양성세포비치여SAH조비교명현강저,차이유통계학의의(P＜0.05).결론 작갑서알가개선SAH소서적인지공능,병가능시통과억제Caspase-3적격활、억제해마신경원적조망기작용.
Objective To investigate the effect and mechanism of methazolamide on cognitive function in spontaneous subarachnoid hemorrhagic (SAH) mice.Methods Ninety male adult C57BL/6J mice were randomly divided into 3 groups:sham group,SAH + vehicle group,and SAH + methazolamide group.SAH model was established by endovascular puncture method,and the blood flow of bleeding cerebral hemisphere was measured by laser Doppler flowmeter.The neurological appraisal and cognitive function were evaluated by Open-field test.The apoptosis of neurons in the hippocampus of the bleeding cerebral hemisphere was examined by using TdT-mediated dUTP nick end labeling (TUNEL) staining.Immunochemistry was used to evaluate the expression level of Caspase-3 in the hippocampus after SAH.Results SAH total mortality was 25.3％.Mortality showed no statistically significant difference between SAH + vehicle group (26.1％) and SAH + methazolamide groups (24.4％).The total distance and Centre time in SAH + methazolamide group at 3rd,7th,and 14th day were significantly increased as compared with SAH + vehicle group at the same time points (P ＜ 0.05).Although the MCA diameter in the sham group (106.89 ± 8.66) was larger than in SAH + vehicle group (87.11 ± 6.73) and SAH + methazolamide group (89.39 ± 7.22,P ＜ 0.05),there was no significant difference between SAH + vehicle group and SAH + methazolamide group (P ＞ 0.05).The TUNEL positive cells rate in the hippocampus in SAH + methazolamide group was lower than in SAH + vehicle group (P ＜ 0.05).The Caspase-3 positive cell rate of in the hippocampus in SAH + methazolamide group was lower than in SAH + vehicle group (P ＜ 0.05).Conclusion Methazolamide can improve cognitive function of SAH mice possibly by inhibiting activation of Caspase-3,and the apoptosis of hippocampal neurons.