基质金属蛋白酶与急性胰腺炎相关性肺损伤的研究  

Study on matrix metalloproteinase-9 and acute pancreas associated lung injury

作　　者：董文珠[1] 李兆申[2] 宋健[1] 鲁青[1] 王群英[1] 张花莲 

机构地区：[1]解放军第401医院消化科,山东青岛266071 [2]第二军医大学附属长海医院消化科

出　　处：《胃肠病学和肝病学杂志》2015年第11期1361-1364,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：上海市卫生系统百名跨世纪优秀学科带头人培养计划(98BR026)

摘　　要：目的探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)在急性胰腺炎相关性肺损伤(acute pancreas associated lung injury,APALI)中的可能作用。方法腹腔注射L-精氨酸制备急性坏死型胰腺炎(acute nerotizing pancreatitis,ANP)模型。82只大鼠随机分为正常对照组(n=6,不做任何处理)、ANP-BB-94治疗组(n=38,40 mg·kg-1·d-1,诱导ANP前腹腔注射BB-94 3次)和ANP组(n=38,40 ml·kg-1·d-1,诱导ANP前腹腔注射生理盐水3次),ANP-BB-94治疗组和ANP组每组10只大鼠观察生存率,其余测定血清淀粉酶、胰腺和肺组织病理评分,明胶酶谱法检测MMP-9活性,检测肺血管Evans blue渗透性,肺脏、胰腺组织的MMP免疫组化研究。结果 ANP-BB-94治疗组生存率较ANP组明显提高,血清淀粉酶、肺的MMP-9活性、蛋白渗漏、MMP-9蛋白含量明显降低(P<0.05)。结论 MMP抑制剂可以明显减轻ANP时胰腺及远处靶器官的损害,为临床治疗APALI、减少ANP死亡率提供了可能的治疗思路。Objective To investigate the changes of matrix metalloproteinase-9 （MMP-9） in acute pancreas associ- ated lung injury （APALI）. Methods Acute nerotizing pancreatitis （ANP） was induced in SD rats by intraperitoneal injection of L-argimne and the consequent pulmonary injury was characterized. Eighty-two male rats were randomized in- to 3 groups： normal control group （n =6） , ANP-BB-94 group （n =38, ANP ＋40 mg kg-1 d-1 BB-9g ip ×3 do- ses） and ANP group （n = 38, ANP ＋ 40 ml kg-1 d-1 normal saline ip × 3 doses） . Additional 10 rats of ANP-BB-94 group and ANP group for survival study were detected. The pancreas and lung were histologically examined by light microscope, and the morphological changes of lung were observed under transmission electron microscope. The contribution of MMP-9 to lung injury was tested with the MMP inhibitor batimastat by Serum amylase and Evans blue. MMP-9 activity and level in homogenates were assessed by zymography and immunohistochemistry. Results MMP activity, amylase level, cellular infiltrate and necrosis were decreased in ANP-BB-94 group compared with ANP group （P 〈0.05）. BB- 94 significantly ameliorated transendothelail neutrophil migration and protein leak in ANP （ P 〈 0.05, P 〈 0.01 ）. BB- 94 improved ANP and APALI, and raised the survival rate. Conclusion Pulmonary and pancreatic injury following ANP can be abrogated by treatment with MMP inhibitor which may result in decreased morbidity and mortality. These findings suggest an important role for MMP-9 in pathogenesis of APALI.

关 键 词：基质金属蛋白酶 胰腺炎 肺损伤 

分 类 号：R576[医药卫生—消化系统]