小白菊内酯调控NF-κB表达改善体外循环犬肺缺血再灌注损伤  

Parthenolide improves pulmonary ischemia-reperfusion injury by regulating the expression of NF-κB in dogs undergoing cardiopulmonary bypass

作　　者：陈松 吴汉华 刘科宇 谢菲 秦莉 张红 Chen Song;Wu Hanhua;Liu Keyu;Xie Fei;Qin Li;Zhang Hong(Department of Anesthesiology,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou,563000,China)

机构地区：[1]遵义医科大学附属医院麻醉科,贵州遵义563000

出　　处：《遵义医科大学学报》2024年第7期659-665,共7页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:82060083);贵州省卫健委科技基金资助项目(NO:gzwjkj2020-1-136);遵义医科大学附属医院硕士启动基金项目[NO:院字(2014)13号]。

摘　　要：目的研究小白菊内酯(PTL)对体外循环(CPB)犬肺缺血再灌注(IR)损伤的影响,并探讨其作用机制。方法18只健康成年中华田园犬,体重10~12 kg,采用随机数字表法分为假手术组(Sham)、肺缺血再灌注组(IR)和小白菊内酯组(PTL)。假手术(Sham)组不进行CPB,其余两组均建立CPB左肺缺血再灌注损伤模型。取CPB前(T_(1))、停机时(T_(2))和实验结束时(T 3)股动脉血行血气分析,计算呼吸指数(RI)和氧合指数(OI);ELSIA检测T_(1)、T_(2)和T_(3)时点血浆和T 3时点左肺肺泡灌洗液中IL-1β、IL-6和TNF-α含量;HE染色观察肺组织病理情况;qRT-PCR检测肺组织TNF-αmRNA表达水平;Western blot检测肺组织NF-κB p65、NF-κB p65和TNF-α蛋白表达水平。结果CPB后犬出现肺损伤,与IR组比较,T_(3)时点PTL组肺组织病理损伤减轻,RI明显降低(P<0.05),血浆、肺泡灌洗液中IL-1β、IL-6和TNF-α含量,肺组织TNF-αmRNA相对表达水平,TNF-α、NF-κB p65蛋白表达水平明显降低(P<0.05),OI明显升高(P<0.05)。结论PTL可改善CPB犬肺损伤,其机制可能与抑制NF-κB p65激活,减轻炎症反应有关。Objective To study the effect of parthenolide on pulmonary ischemia-reperfusion injury in dogs during cardiopulmonary bypass and explore its mechanism.Methods Eighteen healthy adult Chinese rural dogs were randomly devide into sham surgery group(Sham group),pulmonary ischemia-reperfusion group(IR group),and parthenolide group(PTL group)by using a random number table method.The sham group did not undergo CPB,while the other two groups were established CPB left lung ischemia-reperfusion injury models.Artery blood was to collect to perform blood gas analysis and calculate respiratory index(RI)and oxygenation index(OI)at before CPB(T_(1)),stopping CPB(T_(2)),the end of the experiment(T_(3)).ELSIA was used to detect the content IL-1β,IL-6 and TNF-αin plasma at T_(1),T_(2),and T_(3) time points and the content of IL-1β,IL-6 and TNF-αin left alveolar lavage fluid at the end of the experiment(T_(3)),HE staining of lung tissue was used to observe pathological conditions,qRT-PCR was used to detect TNF-αmRNA expression level in lung tissue and western blot was used to detect the protein expression level of NF-κB p65,NF-κB p65 and TNF-αin lung tissue.Results The dog developed lung injury after undergoing CPB.At T3,compared with the CPB group,pathological damage and RI of lung tissue in PTL group were reduced(P<0.05).The content of IL-1β,IL-6 and TNF-αin plasma and bronchoalveolar lavage fluid,the mRNA relative expression level of TNF-α,and the protein expression of NF-κB and TNF-αin PTL group were all reduced(P<0.05),while the OI was increased(P<0.05)in PTL group.Conclusion PTL can improve lung ischemia-reperfusion injury during cardiopulmonary bypass in dogs,and the possible mechanism is related to the inhibition of NF-κB activation and reducing inflammatory response in dogs.

关 键 词：体外循环 肺缺血再灌注损伤 小白菊内酯 核转录因子-ΚB 

分 类 号：R654.1[医药卫生—外科学]