CAJ | 학술논문

目的探讨姜黄素预先给药对大鼠全脑缺血再灌注诱导内质网应激的影响.方法雄性SD大鼠144只,体重200～250 g,月龄2～3月,采用随机数字表法,将大鼠随机分为4组(n=36):假手术组(S组)仅分离双侧颈总动脉;缺血再灌注组(I/R组)采用四血管阻断法制备大鼠全脑缺血再灌注模型;姜黄素组(Cur组)于缺血前1 h腹腔注射姜黄素200 mg/kg;溶媒对照组(VC组)给予等容量姜黄素溶媒--0.5%羧甲基纤维素钠.于再灌注12 h、1、3.7 d时取9只大鼠,取脑,分离海马,采用TUNEL法标记凋亡神经元,计算凋亡指数;采用Western blot法检测海马神经元葡萄糖调节蛋白78(GRP78)、生长停止和DNA损伤诱导基因153(GADDl53)和半胱氨酸天冬氨酸酶-12(caspase-12)的表达水平.结果与S组比较,I/R组和VC组凋亡指数升高,GRP78和caspase-12表达上调(P<0.05);与I/R组比较,Cur组凋亡指数降低,GRP78表达上调,caspase-12表达下调(P<0.05).I/R组、VC组和Cur组间GADD153表达差异无统计学意义(P>0.05).结论姜黄素预先给药可通过抑制内质网应激途径介导的细胞凋亡减轻大鼠全脑缺血再灌注损伤,其机制与海马GRP78表达上调和caspase-12表达下调有关.
목적 탐토강황소예선급약대대서전뇌결혈재관주유도내질망응격적영향.방법 웅성SD대서144지,체중200～250 g,월령2～3월,채용수궤수자표법,장대서수궤분위4조(n=36):가수술조(S조)부분리쌍측경총동맥;결혈재관주조(I/R조)채용사혈관조단법제비대서전뇌결혈재관주모형;강황소조(Cur조)우결혈전1 h복강주사강황소200 mg/kg;용매대조조(VC조)급여등용량강황소용매--0.5%최갑기섬유소납.우재관주12 h、1、3.7 d시취9지대서,취뇌,분리해마,채용TUNEL법표기조망신경원,계산조망지수;채용Western blot법검측해마신경원포도당조절단백78(GRP78)、생장정지화DNA손상유도기인153(GADDl53)화반광안산천동안산매-12(caspase-12)적표체수평.결과 여S조비교,I/R조화VC조조망지수승고,GRP78화caspase-12표체상조(P<0.05);여I/R조비교,Cur조조망지수강저,GRP78표체상조,caspase-12표체하조(P<0.05).I/R조、VC조화Cur조간GADD153표체차이무통계학의의(P>0.05).결론 강황소예선급약가통과억제내질망응격도경개도적세포조망감경대서전뇌결혈재관주손상,기궤제여해마GRP78표체상조화caspase-12표체하조유관.
Objective To investigate the effect of curcumin pretreatment on endoplasmic reticulum stress induced by global cerebral ischemia-reperfusion (I/R) in rats. Methods One hundred forty-four male SD rats weighing 200-250 g were randomly divided into 4 groups (n = 36 each): sham operation group (group S) ; I/Rgroup; curcumin group (group Cur) and vehicle control group (group VC). Global cerebral I/R was produced by four-vessel occlusion technique in S, I/R, Cur, VC groups. Bilateral vertebral arteries were cauterized. Bilateral common carotid arteries were occluded by clipping for 15 min. Curcumin 200 mg/kg was injected intraperitoneally (IP) at 1 h before cerebral ischemia. Global cerebral ischemia was confirmed by unconsciousness and disappearance of papillary and righting reflex. Animals were sacrificed at 12 h, 1,3 and 7 d of reperfusion. Neuronal apoptosis in hippocampal CA1 region was detected by TUNEL assay. Apoptosis index (AI) was calculated. The expression of glucose regulated protein 78 (GRP78) ,growth arrest and DNA damage inducible gene 153 (GADD153) and caspase-12 protein in hippocampal region was assessed by Western blot analysis. Results Cerebral I/R significantly increased AI and GRP78 and caspase-12 protein expression in hippocampus as compared with group S( P <0.05) . Curcumin pretreatment significantly decreased AI, increased GRP78 protein expression and decreased caspase-12 protein expression as compared with group I/R ( P < 0.05) . There was no significant difference in the GADD153 protein expression among Cur, VC and I/R groups ( P > 0.05) . Conclusion Curcumin pretreatment can significantly reduce global cerebral I/R-induced neuronal apoptosis in hippocampus by increasing GRP78 expression and decreasing easpase-12 expression in hippocampus.