青蒿琥酯对小鼠肠缺血再灌注致肺损伤的影响及其与HO-1的关系  

Effect of artesunate on intestinal ischemia/reperfusion-induced lung injury in mice and relationship with heme oxygenase-1

作　　者：季拓 陈萌 叶立 张宗泽[1] 何祥虎[1] Ji Tuo;Chen Meng;Ye Li;Zhang Zongze;He Xianghu(Department of Anesthesiology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院麻醉科,武汉430071

出　　处：《中华麻醉学杂志》2022年第7期862-865,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81000849);武汉大学中南医院科技创新培育基金(znpy2018022);武汉大学中南医院医学科技创新平台建设支撑项目(PTXM2022010)。

摘　　要：目的评价青蒿琥酯对小鼠肠缺血再灌注致肺损伤的影响及其与血红素加氧酶-1(HO-1)的关系。方法SPF级健康雄性C57BL/6小鼠24只,8~9周龄,体重18~22 g,采用随机数字表法分为4组(n=6):假手术组(Sham组)、肠缺血再灌注组(I/R组)、青蒿琥酯组(A组)和青蒿琥酯+HO-1抑制剂锡原卟啉Ⅸ组(AS组)。采用夹闭肠系膜上动脉45 min再灌注2 h的方法建立肠缺血再灌注损伤模型。A组于缺血前1 h经尾静脉注射青蒿琥酯40 mg/kg,AS组于缺血前12 h经尾静脉注射锡原卟啉Ⅸ7.5 mg/kg,缺血前1 h经尾静脉注射青蒿琥酯40 mg/kg。于再灌注2 h时麻醉处死动物,取肺组织,测定湿重/干重(W/D)比值,HE染色光镜下观察病理学结果并进行肺损伤评分,采用比色法测定肺组织髓过氧化物酶(MPO)活性及MDA含量,采用荧光定量PCR法测定肺组织IL-6 mRNA的表达,采用TUNEL法检测细胞凋亡指数(AI)。结果与Sham组比较,I/R组肺损伤评分、W/D比值、MPO活性、MDA含量和AI升高,IL-6 mRNA表达上调(P<0.05);与I/R组比较,A组肺损伤评分、W/D比值、MPO活性、MDA含量和AI降低,IL-6 mRNA表达下调(P<0.05);与A组比较,AS组肺损伤评分、W/D比值、MPO活性、MDA含量和AI升高,IL-6 mRNA表达上调(P<0.05)。结论青蒿琥酯可减轻小鼠肠缺血再灌注致肺损伤,机制可能与激活HO-1有关。Objective To evaluate the effect of artesunate on intestinal ischemia/reperfusion(I/R)-induced lung injury in mice and relationship with heme oxygenase-1(HO-1).Methods Twenty-four healthy SPF male C57BL/6 mice,aged 8-9 weeks,weighing 18-22 g,were divided into 4 groups(n=6 each)using a random number table method:sham operation group(group Sham),intestinal I/R group(group I/R),artesunate group(group A),and artesunate plus HO-1 inhibitor Zinc protoporphyrinⅨ(ZnPP)group(group AS).The model of intestinal I/R injury was established by occluding the superior mesenteric artery for 45 min followed by 2 h reperfusion in anesthetized animals.Artesunate 40 mg/kg was injected via the tail vein at 1 h before ischemia in group A.ZnPP 7.5 mg/kg was injected via the tail vein at 12 h before ischemia,and artesunate 40 mg/kg was injected via the tail vein at 1 h before ischemia in group AS.The animals were sacrificed at the end of reperfusion,and the lung tissues were obtained for microscopic examination of the pathologic changes and for determination of the wet/dry lung weight(W/D)ratio,myeloperoxidase(MPO)activity,malondialdehyde(MDA)content,expression of interleukin-6(IL-6)mRNA(by fluorescence quantitative polymerase chain reaction)and apoptotic index(AI)(by TUNEL).The lung injury score was assessed.Results Compared with group Sham,the lung injury score,W/D ratio,MPO activity,MDA content and AI were significantly increased,and the expression of IL-6 mRNA was up-regulated in group I/R(P<0.05).Compared with group I/R,the lung injury score,W/D ratio,MPO activity,MDA content and AI were significantly decreased,and the expression of IL-6 mRNA was down-regulated in group A(P<0.05).Compared with group A,the lung injury score,W/D ratio,MPO activity,MDA content and AI were significantly increased,and the expression of IL-6 mRNA was up-regulated in group AS(P<0.05).Conclusions Artesunate can alleviate intestinal I/R-induced lung injury,and the mechanism may be related to activation of HO-1 in mice.

关 键 词：青蒿琥酯 血红素加氧酶-1 再灌注损伤 肠 急性肺损伤 

分 类 号：R285.5[医药卫生—中药学]