CAJ | 학술논문

目的探讨DADLE对急性全脑缺血再灌注损伤大鼠脑组织中ERK信号转导通路的影响及其与脑保护作用的关系.方法将健康雌性SD大鼠50只(180 ～ 220 g)随机分为5组:假手术组(Sham,n=10):只暴露血管而不夹闭；缺血再灌注组(I/R,n=10):采用改良的二血管阻断加低血压法建立全脑缺血再灌注模型,缺血15 min后再灌注120 min；DADLE处理组分为DADLE 2 mg/kg组(A,n=10)、DADLE 3 mg/kg组(B,n=10)和DADLE 5 mg/kg组(C,n=10):在I/R组的基础上于再灌注前经颈外静脉注射DADLE.HE染色观察各组海马CAI区神经元病理变化情况,western blot测其脑组织内非磷酸化ERK与磷酸化ERK(P-ERK)的表达状况.结果 Sham组ERK与P-ERK蛋白表达水平显著低于其他各组(P＜0.05)；DADLE处理组与I/R组相比,ERK、P-ERK蛋白的表达水平上调(P＜0.05),其中B组、C组ERK与P-ERK蛋白表达水平显著高于A组(P＜0.05),而B组、C组之间ERK、P-ERK表达则无显著性差异(P＞0.05).结论在急性大鼠全脑缺血再灌注损伤中,ERK信号转导通路的活性明显上调,DADLE可以通过增加ERK的活化而达到降低神经元细胞的损伤,发挥脑保护的作用；同时,该作用呈剂量相关性和有“天花板效应”.
목적 탐토DADLE대급성전뇌결혈재관주손상대서뇌조직중ERK신호전도통로적영향급기여뇌보호작용적관계.방법 장건강자성SD대서50지(180 ～ 220 g)수궤분위5조:가수술조(Sham,n=10):지폭로혈관이불협폐；결혈재관주조(I/R,n=10):채용개량적이혈관조단가저혈압법건립전뇌결혈재관주모형,결혈15 min후재관주120 min；DADLE처리조분위DADLE 2 mg/kg조(A,n=10)、DADLE 3 mg/kg조(B,n=10)화DADLE 5 mg/kg조(C,n=10):재I/R조적기출상우재관주전경경외정맥주사DADLE.HE염색관찰각조해마CAI구신경원병리변화정황,western blot측기뇌조직내비린산화ERK여린산화ERK(P-ERK)적표체상황.결과 Sham조ERK여P-ERK단백표체수평현저저우기타각조(P＜0.05)；DADLE처리조여I/R조상비,ERK、P-ERK단백적표체수평상조(P＜0.05),기중B조、C조ERK여P-ERK단백표체수평현저고우A조(P＜0.05),이B조、C조지간ERK、P-ERK표체칙무현저성차이(P＞0.05).결론 재급성대서전뇌결혈재관주손상중,ERK신호전도통로적활성명현상조,DADLE가이통과증가ERK적활화이체도강저신경원세포적손상,발휘뇌보호적작용；동시,해작용정제량상관성화유“천화판효응”.
Objective To investigate the impact of DADLE on ERK signal transduction pathway in brain tissue in rats with acute global cerebral ischemia-reperfusion injury and the association of DADLE with cerebral protection.Methods Fifty female Sprague-Dawley rats (180-220 g) were randomly divided into 5 groups.Ischemia/reperfusion group (I/R,n =10) was induced by bilateral common artery occlusion combined with hypotension for 15-minute global ischemia followed by 120-minute reperfusion ; sham group (Sham,n =10) exposed bilateral common artery without occlusion; DADLE group was subdivided into DADLE of 2 mg/kg group (A,n =10),DADLE of 3 mg/kg group (B,n =10),and DADLE of 5 mg/kg group (C,n =10).DADLE was applied through external jugular vein before reperfusion.Neuropathological changes in hippocampus CAI area were detected by Hernatoxylin-Eosin (H-E) staining; and the expressions of ERK and phosphorylated ERK (p-ERK) in brain tissue were determined by Western blot.Pesults Expression levels of ERK and p-ERK were significantly lower in sham group than in I/R group and DADLE group (P＜0.05).And the expression levels of ERK and p-ERK were increased in DADLE group as compared with I/R group (P＜0.05).Among the DADLE subgroups,the expression levels of ERK and p-ERK were higher in groups B and C than in group A,but no statistical difference was found between group B and group C.Conclusions DADLE activates ERK signal transduction pathway in brain tissue in rats with acute global cerebral ischemia-reperfusion injury and reduce neuronal cell damage.Tthe neuroprotective action of DADLE is dose-related and has ‘ceiling effect'.