CAJ | 학술논문

目的观察磷脂酰肌醇-3激酶(P13K)抑制剂wortmannin对重症急性胰腺炎(SAP)大鼠的保护及治疗作用并探讨其机制.方法健康成年SD大鼠90只,随机分为对照组、对照+wort-mannin组、SAP组、SAP建模前+wortmannin组及SAP建模后+wortmannin组,每组18只,逆行胆胰管注射50 g/L牛磺胆酸钠制备SAP模型.检测建模后大鼠血清TNF-α水平、血清淀粉酶水平、支气管肺泡灌洗液(BALF)蛋白含量、胰腺组织髓过氧化物酶(MPO)水平;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、血清淀粉酶水平、BALF蛋白含量及胰腺组织MPO水平均显著升高(P<0.01),SAP组胰腺、肺组织病理损伤随病情进展而逐渐加重;SAP建模前+wortmannin组与SAP建模后+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;两组数值间差异无统计学意义(P>0.05);对照+wortmannin组各项指标与对照组相比差异无统计学意义(P>0.05).结论 wortmannin对SAP大鼠有一定的保护及治疗作用,其机制可能包括抑制了胰腺腺泡细胞内P13K的活性,从而一定程度上减轻了钙超载及早期胰蛋白酶原的激活[1];抑制了中性粒细胞(PMN)内P13K信号转导通路的活化,使多种炎症细胞的括化和TNF-α等炎症因子的释放受到抑制.
목적 관찰린지선기순-3격매(P13K)억제제wortmannin대중증급성이선염(SAP)대서적보호급치료작용병탐토기궤제.방법 건강성년SD대서90지,수궤분위대조조、대조+wort-mannin조、SAP조、SAP건모전+wortmannin조급SAP건모후+wortmannin조,매조18지,역행담이관주사50 g/L우광담산납제비SAP모형.검측건모후대서혈청TNF-α수평、혈청정분매수평、지기관폐포관세액(BALF)단백함량、이선조직수과양화물매(MPO)수평;관찰폐조직급이선조직적병리변화.결과 SAP조교대조조혈청TNF-α수평、혈청정분매수평、BALF단백함량급이선조직MPO수평균현저승고(P<0.01),SAP조이선、폐조직병리손상수병정진전이축점가중;SAP건모전+wortmannin조여SAP건모후+wortmannin조교대조조각항지표균승고,단교SAP조균명현강저(P<0.01),이선、폐조직병리손상교SAP조감경;량조수치간차이무통계학의의(P>0.05);대조+wortmannin조각항지표여대조조상비차이무통계학의의(P>0.05).결론 wortmannin대SAP대서유일정적보호급치료작용,기궤제가능포괄억제료이선선포세포내P13K적활성,종이일정정도상감경료개초재급조기이단백매원적격활[1];억제료중성립세포(PMN)내P13K신호전도통로적활화,사다충염증세포적괄화화TNF-α등염증인자적석방수도억제.
Objective To observe the protective and therapeutic effect of wortmannin, inhibitor of phosphatidylinositol 3-kinase (PI3K), on severe acute pancreatitis (SAP) in rats and investigate its mechanism. Methods Ninety SD rats were randomly divided into 5 groups:control group, control+wortmannin group, SAP group, before SAP+ wortmannin group and after 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), serum level of amylase,myeloperoxidase (MPO) activity of pancreatic tissue and the protein content of bronchoalveo-lar lavage fluids (BALF) were evaluated. Histopathological changes of lung and pancreas were ob-served. Results In SAP group, serum level of TNF-α, serum level of amylase, MPO activity of pan-creatic 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 indicators of before SAP + wortmannin group and after SAP+ wortmannin group were also elevated as compared with the con-trol group, but still significantly decreased as compared with SAP group (P<0.01). There was no statistical difference between the two groups. All indicators of control+ wortmannin group and control group had no statistical difference either. Conclusion Pretreatment and treatment with wortmannin could decrease the severity of pancreatitis in rats. The mechanism may be the inhibition on the activity of PI3K in pancreatic acinar cell, thus calcium overload is decreased and the activation of trypsinogen is inhibited to certain extent. Furthermore, there is the inhibition on activation of PI3K in polymorpho-nuclear neutrophils (PMN), further on the activation of many kinds of inflammatory cells and on the release of TNF-a and other inflammatory factors.