黄芪甲苷预处理对大鼠肠缺血再灌注所致肺损伤的影响及其机制  

Effects of astragaloside Ⅳ pre-treatment on lung injury induced by intestinal ischemia-reperfusion in rats

作　　者：王蕾[1] 杨涛 李曼 庞申月 鲁富泰[1] 耿立成[1] WANG Lei;YANG Tao;LI Man(The Department of Anesthesiology,Tianjin Union Medical Center,Tianjin(300191),China)

机构地区：[1]天津市人民医院麻醉科,天津300191

出　　处：《中国中西医结合外科杂志》2023年第1期99-102,共4页Chinese Journal of Surgery of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金青年项目(82102248)。

摘　　要：目的:探讨黄芪甲苷(AS-Ⅳ)预处理对大鼠肠缺血再灌注所致肺损伤的影响及其相关机制。方法:将45只成年雄性SD大鼠随机均分为假手术(sham)组、肠缺血再灌注(I/R)组、AS-Ⅳ预处理(AS-Ⅳ)组。I/R组和AS-Ⅳ组通过夹闭肠系膜上动脉(SMA)60 min后再灌注120 min以建立I/R模型,sham组仅进行SMA暴露处理。AS-Ⅳ组于模型制备前60 min给予AS-Ⅳ(60 mg/kg)灌胃,sham组和I/R组在相同时间点用等体积的生理盐水灌胃。于再灌注120 min时取肺组织,采用HE染色法观察病理学变化,测定肺组织湿/干(W/D)比值和支气管肺泡灌洗液(BALF)/血清中分子量为4 kDa的FITC标记右旋糖酐(FITC-dextran 4 kDa, FD4)比值,并用ELISA法测定肺组织中白细胞介素(IL)-1β和IL-18水平,Western blotting法检测肺组织中NLRP3、ASC和caspase-1表达水平。结果:与sham组比较,I/R组肺组织病理学损伤评分、肺组织W/D比值和BALF/血清FD4比值升高,IL-1β和IL-18水平升高,NLRP3、ASC和caspase-1的表达水平升高(P<0.05);与I/R组比较,AS-Ⅳ组肺脏组织病理学损伤评分、肺组织W/D比值和BALF/血清FD4比值降低,IL-1β和IL-18水平降低,NLRP3、ASC和caspase-1的表达水平降低(P<0.05)。结论:AS-Ⅳ预处理能够显著改善大鼠肠I/R所致的肺损伤,其机制可能与下调NLRP3炎症小体活化水平,减少细胞因子释放,从而减轻肺部组织炎症反应有关。Objective To investigate effects of astragaloside IV(AS-IV) pre-treatment on lung injury induced by intestinal ischemia-reperfusion(I/R) in rats and associated mechanisms. Methods 45 adult male SD rats were randomly divided into 3 groups: sham group, I/R group and AS-IV pre-treatment(AS-IV) group. Intestinal I/R model was established by clipping superior mesenteric artery for 60 min and subsequent reperfusion for 120min in I/R group and AS-IV group. Rats received intragastric administration with 60 mg/kg AS-Ⅳ 60 min before I/R in AS-IV group. At 120 min after I/R, pathological changes and scores of lung tissues were detected via H-E staining;The wet/dry weight(W/D) ratio of lung tissues and bronchoalveolar lavage fluids(BALF)/serum FITCdextran 4 kDa(FD4) ratio were measured;expression levels of IL-1β and IL-18 were assessed by ELISA assay;expression levels of NLRP3, ASC and caspase-1 were detected via westernblot assay. Results Compared with sham group, pathological injury scores, W/D ratio, BALF/serum FD4 ratio, expression levels of IL-1 β, IL-18,NLRP3, ASC and caspase-1 were increased in I/R group(P<0.05). Compared with I/R group, pathological injury scores, W/D ratio, BALF/serum FD4 ratio, expression levels of IL-1β, IL-18, NLRP3, ASC and caspase-1 were decreased in AS-IV group(P<0.05). Conclusion AS-IV pre-treatment can significantly attenuate lung injury induced by intestinal I/R in rats, which is associated with down-regulating inflammation in lung tissues via suppressing NLRP3 inflammasome activation.

关 键 词：黄芪甲苷 缺血再灌注 肺损伤 NLRP3炎症小体 炎性因子 

分 类 号：Q95-33[生物学—动物学] R619[医药卫生—外科学]