CAJ | 학술논문

目的探讨磷脂酰肌醇-3激酶(PI3K)抑制剂喔漫青霉素(Wortmannin)在重症急性胰腺炎(SAP)肺损伤时对肺的保护作用及其作用机制.方法将健康成年雄SD大鼠56只随机分为假手术(SO)组、SAP组、SAP+ Wortmannin( SAP+W)组,胰胆管逆行注入4％牛磺胆酸钠法建立SAP模型.动态检测肺含水率、髓过氧化物酶(MPO)、基质金属蛋白酶-9(MMP-9)、蛋白激酶B(PKB)、磷酸化蛋白激酶B(p-PKB)活性,观察胰腺、肺组织病理学变化.结果 SAP组建模后3h肺组织p-PKB表达开始上升,至12h达最高,较SO组明显升高(582.95±34.72比191.34±39.53)(P＜0.05)；肺含水率、MPO、MMP-9活性也逐渐升高,肺损伤程度逐渐加重(P＜0.05)；SAP+W组肺组织p-PKB表达3h后开始上升,至12 h达最高,较SO组升高(455.65±40.47比191.34±39.53) (P ＜0.05),但较SAP组明显降低(455.65±40.47比582.95±34.72)(P＜0.05),其余指标也较SAP组减轻.结论 Wortmannin对SAP时肺损伤有一定保护作用,其机制可能与抑制了中性粒细胞内PI3K通路活性,减少中性粒细胞活化、迁移,及抑制炎性因子如MMP-9等的释放有关.
목적 탐토린지선기순-3격매(PI3K)억제제악만청매소(Wortmannin)재중증급성이선염(SAP)폐손상시대폐적보호작용급기작용궤제.방법 장건강성년웅SD대서56지수궤분위가수술(SO)조、SAP조、SAP+ Wortmannin( SAP+W)조,이담관역행주입4％우광담산납법건립SAP모형.동태검측폐함수솔、수과양화물매(MPO)、기질금속단백매-9(MMP-9)、단백격매B(PKB)、린산화단백격매B(p-PKB)활성,관찰이선、폐조직병이학변화.결과 SAP조건모후3h폐조직p-PKB표체개시상승,지12h체최고,교SO조명현승고(582.95±34.72비191.34±39.53)(P＜0.05)；폐함수솔、MPO、MMP-9활성야축점승고,폐손상정도축점가중(P＜0.05)；SAP+W조폐조직p-PKB표체3h후개시상승,지12 h체최고,교SO조승고(455.65±40.47비191.34±39.53) (P ＜0.05),단교SAP조명현강저(455.65±40.47비582.95±34.72)(P＜0.05),기여지표야교SAP조감경.결론 Wortmannin대SAP시폐손상유일정보호작용,기궤제가능여억제료중성립세포내PI3K통로활성,감소중성립세포활화、천이,급억제염성인자여MMP-9등적석방유관.
Objective To investigate the protective effect and mechanism of phosphatidylinositol-3 kinase (PI3K) inhibitor Wortmannin in severe acute pancreatitis (SAP) associated with acute lung injury.Methods Fifty-six rats were randomly divided into 3 groups:sham operation (SO) group ( n =8 ),SAP group (n =24),and SAP + Wortmannin (SAP + W) group (n =24).SAP model was induced by retrograde injection of 4％ sodium taurocholate into the biliopancreatic duct of rats.The rate of lung water content,myeloperoxidase ( MPO ),matrix metalloproteinase-9 ( MMP-9 ),protein kinase B ( PKB ),abd phosphorylation of protein kinase B (p-PKB) activity in the lung tissue were evaluated.Results In SAP group,the p-PKB expression in the lung tissue began to rise at 3 h after modeling,and reached the peak at 12 h (582.95 ±34.72 vs 191.34 ±39.53) (P ＜0.05) ; the rate of lung water content,MPO,and MMP9 activity were also gradually increased,and the degree of lung lesion gradually increased ( P ＜ 0.05 ) ; in SAP + Wortmannin group,the p-PKB expression in the lung tissue began to rise at 3 h after modeling,reached the peak at 12 h,and higher than in SO group (455.65 ± 40.47 vs 191.34 ± 39.53) (P ＜0.05),but significantly lower than that in SAP group (455.65 ±40.47 vs 582.95 ±34.72) (P ＜0.05).The rest indicators in SAP + Wortmannin group were also significantly decreased as compared with SAP group ( P ＜ 0.05 ).Conclusion Pretreatment with wortmannin could decrease the lung lesion of rats with SAP probably by inhibiting the activation of phosphatidylinositol 3-kinase signal transduction pathway in polymorphonuclear neutrophils (PMN),reducing PMN activation and migration,further more,suppressing the release of MMP-9 and other inflammatory factors.