急性坏死性胰腺炎大鼠心肌核因子-κB激活及重组葡激酶的干预作用

Myocardial NF-κB activity in SAP rats and intervention effect of recombinant staphylokinase

目的研究重症急性胰腺炎(SAP)心肌功能损害时心肌核因子-κB(NF-κB)的活化及葡激酶的干预作用。方法63只SD大鼠随机分为假手术组(n=9)、ANP组(n=27)、葡激酶干预组(n= 27),ANP模型采用5％的牛磺胆酸钠胰胆管逆行注射方法建立。干预自造模前2 d腹腔注射葡激酶1．5 mg／kg体重,一天2次,共4次。ELISA法测定制模后6 h、12 h、24 h各时点血TNF-α、IL-6含量;RT- PCR检测心肌NF-κB mRNA的表达;免疫组化法检测心肌NF-κB蛋白的表达,常规观察胰腺及心肌组织的病理变化。结果ANP组术后6 h大鼠心肌NF-κB mRNA及NF-κB蛋白表达异常增高,TNF-α、IL-6呈进行性升高,干预组胰腺及心肌组织的病理变化减轻。心肌NF-κB mRNA及蛋白表达下词,血TNF-α、IL-6明显下降,与ANP组比较,差异均显著(P<0．05)。结论ANP大鼠的心肌损伤可能与循环中TNF-α、IL-6水平升高导致的心肌NF-κB活化有关。葡激酶对SAP并发的心肌损伤具有防治作用。

Objective To investigate myocardial NF-κB mRNA activity in severe acute pancreatitis and the intervention effect of the recombinant staphylokinase on damaged myocardium. Methods Sixty-three male SD rats were divided randomly into the sham-operated group （n - 9）, the acute neoplastic pancreatitis （ANP） group （n = 27） and the recombinant staphylokinase treatment group （n = 27）. Acute neoplastic pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Artery blood of the each group was obtained at 6 h, 12 h and 24 h after induction of ANP. Serum concentrations of TNF-α and IL-6 were measured by ELISA. The expression of NF-κB mRNA in myocardial tissue was evaluated by RT-PCR. NF-κB protein in myocardial tissue was determined by SP immunohistochemstry. Pancreatic and myocardial tissues were stained with HE and examined under light microscopy. Results The myocardial NF-κB expression and the serum levels of TNF- α and IL-6 was significantly increased at 6 hours after induction of ANP. In the treatment group, expression of myocardial NF-κB and serum levels of TNF-αand IL-6 were significantly decreased, comparing with those of the ANP group （P 〈 0.05）. Pathological changes of pancreatic and myocardial tissues in the treatment group were alleviated in contrast to the ANP group. Conclusions The myocardial damage in rats with ANP might attribute to myocardial NF-κB activation resulted from increase TNF- α and IL-6 in blood circulation. The staphylokinase have a beneficial role in the prevention and therapy for SAP associated myocardial damage.