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目的探讨磷酸肌酸钠治疗新生儿窒息致心脏损害的疗效和可能机制。方法 (1)将67例新生儿窒息致心脏损害患儿随机分为观察组和对照组,对照组接受常规治疗,观察组给予磷酸肌酸钠,观察两组治疗有效率和心肌酶谱变化。(2)将80只SD大鼠随机分为假手术组(Sham组)、缺血组(IS组)、磷酸肌酸纳组(CP组)、对照组(NS组),通过结扎SD大鼠冠状动脉左前降支构建心肌缺血模型,HE染色观察心肌细胞病理变化,TUNEL染色检测细胞凋亡,蛋白质印迹(Western blot)、聚合酶链反应(Real-time PCR)检测心肌组织fas基因的表达。结果 (1)观察组总有效率77.78%(28/36)高于对照组总有效率45.16%(14/31),差异有统计学意义(χ~2=7.576,P=0.005 9),观察组心电图(ECG)正常例数多于对照组,差异有统计学意义(χ~2=5.135,P=0.023 5),观察组肌酸肌酶(CK)、肌酸肌酶同工酶(CK-MB)、心肌肌钙蛋白(eTnI)、乳酸脱氢酶(LDH)低于对照组,差异有统计学意义(t=12.44、10.24、18.50、7.956,P<0.05)。(2)CP组SD大鼠死亡率低于IS组(χ2=5.715,P=0.016 8)和NS组(χ~2=4.445,P=0.035 0),差异有统计学意义,CP组SD大鼠心肌细胞凋亡指数低于IS组和NS组(F=44.96,P<0.000 1),CP组fas mRNA表达低于IS组和NS组(F=14.28,P<0.000 1),CP组fas蛋白表达低于IS组、NS组(F=154.8,P<0.000 1),差异有统计学意义。结论磷酸肌酸钠能够减轻新生儿窒息后心肌的损伤,磷酸肌酸钠通过减少fas基因表达,减少心肌细胞凋亡。
Objective To investigate the efficacy and possible mechanism of sodium creatine phosphate in treating neonatal asphyxia-induced cardiac damage. Methods (1) Sixty-seven neonates with asphyxia caused cardiac damage were randomly divided into observation group and control group. The control group received routine treatment. The observation group was treated with sodium creatine phosphate. The therapeutic efficiency and myocardial zymogram were observed. (2) Eighty SD rats were randomly divided into Sham group, IS group, CP group and control group (NS group) The left anterior descending coronary artery was used to establish the model of myocardial ischemia. The pathological changes of myocardial cells were observed by HE staining. The apoptosis of myocardial cells was detected by TUNEL staining. The expression of fas gene in myocardium was detected by Western blot and Real-time PCR . Results The total effective rate in the observation group was 77.78% (28/36), which was significantly higher than that in the control group (45.16%, 14/31) (χ ~ 2 = 7.576, P = 0.005 9) There were significant differences between the two groups (χ ~ 2 = 5.135, P = 0.023 5). The CK, MB and CK in the observation group were higher than those in the control group ), Cardiac troponin (eTnI) and lactate dehydrogenase (LDH) were lower than the control group (t = 12.44,10.24,18.50,7.956, P <0.05). (2) The mortality of SD rats in CP group was significantly lower than that in IS group (χ2 = 5.715, P = 0.0168) and NS group (χ2 = 4.445, P = 0.035 0) The apoptosis index of cardiomyocytes was lower in IS group and NS group than in IS group and NS group (F = 44.96, P <0.0001). The fas mRNA expression in CP group was lower than that in IS group and NS group (F = 14.28, P <0.0001) The protein expression was lower than IS group and NS group (F = 154.8, P <0.000 1), the difference was statistically significant. Conclusion Sodium creatine phosphate can attenuate cardiac damage in neonates with asphyxia. Sodium creatine phosphate reduces cardiomyocyte apoptosis by decreasing fas expression.