wortmannin对重症急性胰腺炎大鼠肺损伤的保护作用

Protective effect of wortmannin against lung injuries induced by severe acute pancreatitis in rats

目的:观察磷脂酰肌醇-3激酶(PI3K)抑制剂wort-mannin对重症急性胰腺炎(SAP)大鼠肺损伤的保护作用并探讨其机制.方法:将健康成年SD大鼠54只随机分为对照组、SAP组和SAP+wortmannin组,每组18只,逆行胆胰管注射50g/L牛磺胆酸钠制备SAP模型.检测血清TNF-α水平、肺组织湿/干质量比值、肺组织髓过氧化物酶(MPO)活性、支气管肺泡灌洗液(BALF)蛋白含量;观察肺组织及胰腺组织的病理变化.结果:SAP组较对照组血清TNF-α水平、肺组织湿/干质量比值、BALF蛋白含量及肺组织MPO活性均显著升高(P<0.01),胰腺、肺组织病理损伤随病情进展而逐渐加重;SAP+wortmannin组较对照组各项指标均升高,但较SAP组均明显降低(P<0.01),胰腺、肺组织病理损伤较SAP组减轻.结论:wortmannin对SAP大鼠肺损伤有一定的保护作用,其机制可能与其抑制了中性粒细胞内PI3K信号转导通路的活化,使多种炎症细胞的活化和TNF-α等炎症因子的释放受到抑制有关.

AIM： To observe the protective effect of wortmannin against lung injuries indued by severe acute pancreatitis （SAP） in rats and investigate its mechanism. METHODS： Fifty-four SD rats were randomly divided into 3 groups： control group, SAP group and SAP ＋ wortmannin group （n = 18 per group）, SAP model was induced by retrograde infusion of 50 g/L sodium taurocholate into the biliopancreatic duct of rats. Serum level of tumor necrosis factor-alpha （TNF-α）, lung wet/dry weight ratio, myelopemxidase （MPO） activity of lung tissue and the protein content of bronchoalveolar lavage fluids （BALF） were evaluated; histopathology of lung and pancreas were studied. RESULTS： In SAP group, serum level of TNF-α, lung wet/dry weight ratio, MPO activity of lung tissues and the protein content of BALF were significantly elevated （P 〈0.01 ） ; the lung and pancreas injuries were gradually aggravated with disease progression. All the indi- cators of SAP ＋ wortmannin group were also elevated as compared with control group, but still significantly decreased as compared with SAP group （ P 〈0.01 ）. CONCLUSION： Pretreatment with wortmannin could decrease the lung lesion of pancreatitis rats. The mechanism may be ralated to the inhibition on the activation of phosphatidylinositol 3-kinase signal transduction pathway in polymorphonuclear neutrophils （PMN）, further more, on the activation of many kinds of inflammatory cells and on the release of TNF-α and other inflammatory factors.