重组葡激酶对重症急性胰腺炎大鼠心肌损伤的治疗作用

Effect of recombinant staphylokinase on inhibiting rats' myocardial damage following severe acute pancreatitis

[目的]研究重组葡激酶(r-Sak)对大鼠重症急性胰腺炎(SAP)的发展及心肌损伤的干预作用,探讨其作用机制。[方法]63只SD大鼠随机分为假手术(A)组(n=9),模型对照(B)组(n=27),r-Sak治疗(C)组(n=27)。SAP模型采用5%牛磺胆酸钠胰胆管逆行注射方法建立。ELISA法测定6、12、18 h各时点血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、肌酸激酶同工酶(CK-MB)及心肌肌钙蛋白(CTn1)水平,免疫组化法检测术后6、121、8 h各时点心肌核转录因子-κB(NF-κB)的活化情况,光镜及电镜下观察胰腺及心肌组织的病理变化。[结果]大鼠从术后6 h开始出现CTn1、CK-MB升高,治疗组各时点较对照组明显下降(P<0.05)。IL-6、TNF-α水平亦从术后6 h开始升高,其变化在时点上与CTn1、CK-MB的变化具有一致性,治疗组各时点与对照组相比明显下降(P<0.05)。治疗组胰腺及心肌组织的出血坏死减轻,微血管血栓的形成减少。[结论]r-Sak能减轻SAP的病变程度和心肌损伤,可能具有治疗SAP及预防心肌损伤等并发症的作用,特异性溶栓剂的应用可能成为治疗SAP的新途径。

[Objective]To investigate the effect of recombinant staphylokinase（r Sak）on severe acute pancreatitis （SAP） and severe acute pancreatitis associated myocardial damage. [Methods]： Sixty three male SD rats were divided randomly into the sham-operated group （group A,n=9）, the control group （group B, n=27） and the r-Sak treatment group （group C, n=27）. SAP wasinduced by intraductal administration 5% sodium taurocholate. Artery blood of group A, B and C was obtained at 6h, 12h and 18h after induction of the model. Serum contents of TNFα, IL-6 and CK-MB, CTnl were detected with ELISA. The activity of NF-κB in myocardial tissue was determined by SP immunohistochemical technique. Pancreatic and myocardial tissues were examined under light and electron microscopy. [Result] ： The contents of CTn1, CK-MB in serum was significantly increased in 6 hours after induction of SAP, and the serum levels of TNF- α and IL- 6 were also elevated at the same time. The contents of the CTnl, CK-MB and TNF- α, IL-6 in serum were significantly decreased, compared with those of the control group （P〈0. 05）. The pathological changes of pancreatic and myocardial tissues in the treatment group were alleviated in contrast to the control group. [Conelusion]： R-Sak can lighten the pathological changes of SAP rats, and alleviate myocardial damage following SAP. R-Sak is a promising agent for SAP therapy and the application of thrombolytic agents would be a new strategy for SAP therapy.