氯膦酸二钠脂质体对大鼠重症急性胰腺炎肺损伤的影响及与Akt、MAPK(ERK1/2)通路的关系  

Alleviative effect of liposomal clodronate against lung injury in rats with severe acute pancreatitis and its relations with Akt and MAPK(ERK1/2) pathways

作　　者：李涛[1] 刘源[1] 李冉[1] 刘路路[1] 蒋国雄[1] 党胜春[1] 张建新[1] 顾敏 

机构地区：[1]江苏大学附属医院普通外科,江苏镇江212001 [2]江苏省镇江市中西医结合医院,江苏镇江212002

出　　处：《中国普通外科杂志》2016年第3期350-356,共7页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(81070287);江苏省自然科学基金资助项目(BK2012704);江苏省镇江市社会发展科技支撑资助项目(SH2013022;SH2014089)

摘　　要：目的:探讨氯膦酸二钠脂质体(LC)对大鼠重症急性胰腺炎(SAP)肺损伤的影响及与Akt、MAPK(ERK1/2)通路的关系。方法:将48只SD大鼠随机均分为假手术组、SAP模型组(模型组)、SAP模型+LC处理组(LC组),后两组采用膜下注射5%牛磺胆酸钠制作SAP模型,并分别于造模后尾静脉注射空白脂质体与LC。各组分别于术后2、6h后检测血清淀粉酶(AMS)、IL-6、TNF-α的含量,观察肺组织病理学变化,及肺组织中Akt和MAPK(ERK1/2)的表达。结果:与假手术组比较,模型组与LC组血清AMS、IL-6及TNF-α含量、肺组织病理学评分,肺组织Akt和MAPK(ERK1/2)表达水平均明显升高,且均随时间延长而更加明显(均P<0.05),但LC组的上述指标在各时间点上均明显低于模型组(均P<0.05)。结论:LC有减轻大鼠SAP肺损伤的作用,机制可能与肺泡巨噬细胞吞噬LC后,Akt和MAPK(ERK1/2)信号通路抑制,从而减少炎症细胞因子的释放有关。Objective： To investigate the effect of liposomal clodronate（LC） on lung injury secondary to severe acute pancreatitis（SAP） in rats and its relations with Aktand MAPK（ERK1/2） pathways. Methods： Forty-eight SD rats were equally randomized into sham operation group, SAP model group（model group） and SAP model plus LC treatment group（LC group）, and in the latter two groups, SAP model was created by injection of 5% sodium taurocholate beneath the pancreatic capsule, and after that were given naked liposome and LC respectively by tail vein injection. In each group at 2 and 6 h after operation, the serum levels of amylase（AMS）, IL-6, and TNF-αweremeasured, and pathological changes, as well as Akt and MAPK（ERK1/2） expressions in the lung tissue were observed. Results： In both model group and LC group compared with sham operation group, the serum levels of AMS, IL-6 and TNF-α,the pathological score, and the expression levels of Akt and MAPK（ERK1/2） were significantly increased, and all became evident as time went on（all P〈0.05）, but all above parameters in LC group were significantly lower than those in model group at each time point（all P〈0.05）. Conclusion： LC has alleviative effect against SAP-induced lung injury in rats, and the mechanism may be associated with reduced inflammatory factors that result from inhibition of Akt and MAPK（ERK1/2） signaling pathways after LC uptake by alveolar macrophages.

关 键 词：胰腺炎 急性坏死性 肺损伤 氯膦酸 巨噬细胞 肺泡 

分 类 号：R657.5[医药卫生—外科学]