依达拉奉联合参麦注射液对窒息新生大鼠的心肌保护作用

Protective Effect of Edaravone Combined with Shenmai Injection on Myocardia of Rats with Neonatal Asphyxia

目的探讨依达拉奉联合参麦注射液对窒息新生大鼠心肌的作用效果及其可能的机制。方法将50只7日龄新生SD大鼠按随机数字表法分为A组(阴性对照组)、B组(阳性对照组)、C组(依达拉奉组)、D组(参麦注射液组)、E租(依达拉奉联合参麦注射液组),每组10只。B、C、D、E组大鼠制备常压窒息模型。制模成功后,A、B、C、D、E组分别腹腔注射生理盐水4 mL·kg^(-1)、生理盐水4 mL·kg^(-1)、依达拉奉2 mL·kg^(-1)及生理盐水2 mL·kg^(-1)、参麦注射液2 mL·kg^(-1)及生理盐水2 mL·kg^(-1)、依达拉奉2 mL·kg^(-1)及参麦注射液2 mL·kg^(-1)。复氧120min后立即取标本(血液、心肌组织),比较各组血清肌酸激酶(CK)、乳酸脱氢酶(LDH)水平及心肌组织磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)、b细胞淋巴瘤/白血病-2(Bcl-2)蛋白表达水平,观察各组心肌病理形态学改变与细胞凋亡情况。结果与A组比较,B、C、D、E组血清CK与LDH水平、心肌组织p-p38MAPK与Bcl-2蛋白表达水平及心肌细胞凋亡数均显著升高(P<0.01)。与B组比较,C、D、E组血清CK与LDH水平、心肌组织p-p38MAPK蛋白表达水平及心肌细胞凋亡数均显著降低(P<0.01),而Bcl-2蛋白表达水平均显著升高(P<0.01)。C、E组血清CK水平、心肌组织p-p38MAPK蛋白表达水平及心肌细胞凋亡数均较D组明显降低(P<0.05),但上述指标C组与E组比较差异均无统计学意义(P>0.05)。C、D、E组3组间血清LDH水平、心肌组织Bcl-2蛋白表达水平比较差异均无统计学意义(P>0.05)。结论依达拉奉、参麦注射液均可通过减少p38MAPK的活化,上调Bcl-2蛋白水平,减少窒息新生大鼠心肌细胞凋亡,起到心肌保护作用;单用依达拉奉与依达拉奉联合参麦注射液治疗其疗效无明显差异。

Objective To investigate the protective effect of edaravone combined with Shenmai injection on myocardia of neonatal rats with asphyxia,and to explore the potential mechanisms. Methods Totally 50 7-day-old Sprague-Dawleyrats were randomly divided into A,B,C,D,E groups,with 10 rats in each group.After asphyxia was successfully induced,rats in groups B,C,D and E were treated withnormal saline(4 mL·kg^-1 ),edaravone(2 mL·kg^-1 )+normal saline(2 mL·kg^-1 ),Shenmai injection (2 mL·kg^-1 )+normal saline(2 mL·kg^-1 ),and edaravone(2 mL·kg^-1 )+Shenmai injection(2 mL·kg^-1 ),respectively.The group A was selected as the negative control and only received normal saline(4 mL·kg^-1 ).Blood and myocardium samples were collected 120 minutes after reoxygenation.Serum levels of creatine kinase (CK) and lactic dehydrogenase (LDH),myocardial expression of p-p38MAPK and Bcl-2,histopathological changes,and myocardial apoptosis were compared among the five groups. Results Compared with group A,serum CK and LDH levels,myocardial p-p38MAPK and Bcl-2 proteins expression and the number of apoptotic of myocardial cells in groups B,C,D and E were significantly increased( P <0.01).Compared with group B,serum CK and LDH levels,myocardial p-p38MAPK proteins expression and the number of apoptotic of myocardial cells in groups C,D and E were significantly reduced( P <0.01),but the expression of myocardial Bcl-2 protein increased significantly( P <0.01).Compared with group D,serum CK levels,myocardial p-p38MAPK expression and myocardial apoptosis were reduced in groups C and E ( P <0.05).However,these indexes were not statistically different between group C and group E ( P >0.05).Moreover,there were no significant differences in serum LDH levels and myocardial Bcl-2 expression among groups C,D and E ( P >0.05). Conclusion Both edaravone and Shenmai injection reduce myocardial apoptosis in neonatal rats with asphyxia through inhibiting p38MAPK activation and up-regulating Bcl-2 protein expression.However,their combination is not more effective than edaravone alone.