CAJ | 학술논문

目的评价布托啡诺预先给药对肢体缺血再灌注致大鼠心肌损伤的影响.方法健康雄性SD大鼠108只,体重180～220 g,采用随机数字表法,将其分为3组(n=36):假手术组(S组)、缺血再灌注组(I/R组)和布托啡诺预先给药组(B组).I/R组和B组采用夹闭双侧股动脉2h恢复灌注的方法制备后肢缺血再灌注诱发大鼠心肌损伤模型.B组缺血前10 min右颈内静脉注射布托啡诺注射液0.2 mg/kg,I/R组右颈内静脉注射等量生理盐水.各组于缺血前即刻(T0)、再灌注2 h(T1)、6h(T2)、12 h(T3)、24 h(T4)和48 h(T5)时随机取6只大鼠取腹主动脉血样,采用ELISA法测定血清肌酸激酶同工酶(CK-MB)活性、心肌肌钙蛋白Ⅰ(cTnI)浓度;随后处死大鼠,取心肌组织,采用TUNEL法检测心肌凋亡细胞,计算心肌细胞凋亡指数;采用Western blot法测定心肌细胞c-Jun氨基末端激酶(JNK)和细胞外调节蛋白激酶(ERK)的表达水平.结果与S组比较,I/R组T1-5时血清CK-MB和cTnI水平升高,T2-5时心肌细胞凋亡指数、心肌组织ERK和JNK的表达水平升高(P＜0.05);与I/R组比较,B组T4时心肌病理学损伤减轻,T2-5时血清CK-MB和cTnI水平降低,T4,5时心肌细胞凋亡指数降低,T2-5时心肌组织ERK的表达水平升高,T2-4时JNK的表达水平降低(P＜0.05).结论布托啡诺预先给药通过激活MAPK信号传导通路,上调ERK和下调JNK表达,减少心肌细胞凋亡,从而减轻肢体缺血再灌注致大鼠的心肌损伤.
목적 평개포탁배낙예선급약대지체결혈재관주치대서심기손상적영향.방법 건강웅성SD대서108지,체중180～220 g,채용수궤수자표법,장기분위3조(n=36):가수술조(S조)、결혈재관주조(I/R조)화포탁배낙예선급약조(B조).I/R조화B조채용협폐쌍측고동맥2h회복관주적방법제비후지결혈재관주유발대서심기손상모형.B조결혈전10 min우경내정맥주사포탁배낙주사액0.2 mg/kg,I/R조우경내정맥주사등량생리염수.각조우결혈전즉각(T0)、재관주2 h(T1)、6h(T2)、12 h(T3)、24 h(T4)화48 h(T5)시수궤취6지대서취복주동맥혈양,채용ELISA법측정혈청기산격매동공매(CK-MB)활성、심기기개단백Ⅰ(cTnI)농도;수후처사대서,취심기조직,채용TUNEL법검측심기조망세포,계산심기세포조망지수;채용Western blot법측정심기세포c-Jun안기말단격매(JNK)화세포외조절단백격매(ERK)적표체수평.결과 여S조비교,I/R조T1-5시혈청CK-MB화cTnI수평승고,T2-5시심기세포조망지수、심기조직ERK화JNK적표체수평승고(P＜0.05);여I/R조비교,B조T4시심기병이학손상감경,T2-5시혈청CK-MB화cTnI수평강저,T4,5시심기세포조망지수강저,T2-5시심기조직ERK적표체수평승고,T2-4시JNK적표체수평강저(P＜0.05).결론 포탁배낙예선급약통과격활MAPK신호전도통로,상조ERK화하조JNK표체,감소심기세포조망,종이감경지체결혈재관주치대서적심기손상.
Objective To evaluate the effects of butorphanol pretreatment on myocardial damage induced by limb ischemia/reperfusion (I/R) in rats.Methods One hundred and eight male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =36 each) using a random number table:sham operation group (group S),I/R group and butorphanol pretreatment group (group B).Limb ischemia was induced by occlusion of bilateral hind limbs for 2 h followed by reperfusion in I/R and B groups.At 10 min before ischemia,butorphanol 0.2 mg/kg was injected via the right jugular vein in group B,while the equal volume of normal saline was injected in group I/R.Six rats were chosen randomly before ischemia (baseline,T0) and at 2,6,12,24 and 48 h after reperfusion (T1-5) and blood samples were taken from the abdominal aorta for determination of the serum creatine kinase isoenzyme-MB (CK-MB) activity and cardiac troponin Ⅰ (cTnI) concentration.The animals were then sacrificed and myocardial specimens were obtained for determination of myocardial apoptosis (using TUNEL) and the expression of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) (using Western blot analysis).Apoptosis index was calculated.Results Compared with group S,the serum CK-MB and cTnI levels were significantly increased at T1-5,and the apoptosis index and expression of JNK and ERK were increased at T2-5 in group I/R (P ＜ 0.05).Compared with group I/R,the pathological changes of myocardium were significantly reduced at T4,the serum CK-MB and cTnI levels were decreased at T2-5,the apoptosis index was decreased at T4,5,the expression of ERK was up-regulated at T2-5,and the expression of JNK was down-regulated at T2-4 (P ＜ 0.05).Conclusion Butorphanol pretreatment can reduce apoptosis in myocardial cells through activating MAPK signal transduction pathway,up-regulating ERK expression and down-regulating JNK expression,thus attenuating myocardial damage induced by limb I/R in rats.