阿格拉宾对小鼠肺缺血再灌注损伤的保护作用及机制  

Protective Effect and Mechanism of Arglabin on Murine Lung Ischemia-reperfusion Injury

作　　者：周倩 胡晓晴[1] 熊娟[1] 范国华[1] ZHOU Qian;HU Xiaoqing;XIONG Juan(Department of Thoracic Surgery,Renmin Hospital of Wuhan University,Hubei 430061,China)

机构地区：[1]武汉大学人民医院胸外科,430061

出　　处：《医学研究杂志》2022年第11期77-81,共5页Journal of Medical Research

基　　金：湖北省自然科学基金资助项目(2020cfb609)。

摘　　要：目的观察阿格拉宾在小鼠肺缺血再灌注损伤中的作用并探讨可能机制。方法根据随机数表法将40只8~10周龄雄性C57/B6小鼠随机分为4组,即对照组、阿格拉宾组、缺血再灌注组和治疗组。采用左肺门夹闭1h,再灌注2h的方式构建小鼠肺缺血再灌注损伤模型,治疗组小鼠在肺门夹闭前1h给予阿格拉宾(5μg/kg)腹腔注射。再灌注结束后,留取左肺组织行HE染色评估肺损伤状况,同时Western blot法检测炎性因子[白细胞介素-1β(interleukin-1β,IL-1β),单核细胞趋化因子-1(monocyte chemoattractant protein-1,MCP-1),肿瘤坏死因子(tumor necrosis factor,TNF)-α]、焦亡标志物[NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)和凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a caspase-recruitment domain,ASC)]及自噬相关蛋白(Beclin1和ATG7)的表达。结果缺血再灌注组较对照组小鼠肺组织病理损伤明显加重,肺组织炎性因子IL-1β、MCP-1和TNF-α相对表达明显升高(P均<0.05),焦亡相关标志蛋白NLPR3和ASC的表达水平明显升高(P均<0.05),同时自噬相关蛋白Beclin1和ATG7被明显抑制(P均<0.05);予以阿格拉宾预处理后,肺缺血再灌注小鼠肺病理损伤明显减轻、肺组织炎性因子IL-1β、MCP-1和TNF-α相对表达明显降低(P均<0.05);焦亡相关标志蛋白NLPR3和ASC的表达水平明显降低(P均<0.05),自噬相关蛋白Beclin-1和ATG7被明显上调(P均<0.05)。结论阿格拉宾可能通过抑制焦亡并激活自噬改善小鼠肺缺血再灌注损伤。Objective To observe the effect of Arglabin on murine lung ischemia-reperfusion injury and explore the possible mechanism.Methods According to the random number table,40male C57/B6mice aged 8-10 weeks were randomly divided into 4groups,namely the control group,the Arglabin group,the ischemia-reperfusion group and the treatment group.The mouse model of lung ischemia-reperfusion injury was established by clipping the left hilum for 1h and reperfusion for 2h.The mice in the treatment group were given an intraperitoneal injection of Arglabin(5μg/kg)1h before the hilar clip.After reperfusion,the left lung tissue was collected for HE staining,and the relative expression levels of related proteins including interleukin-1β(IL-1β),monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α),NLRP3,ASC,Beclin1 and ATG7 were detected by western blot.Results Compared with the control group,the ischemia-reperfusion group significantly increased lung pathological injury,increased expression levels of inflammatory proteins IL-1β,MCP-1 and TNF-α,significantly increased the expression levels of pyroptosis-related marker proteins NLPR3 and ASC,and significantly inhibited the level of autophagy Beclin-1 and ATG7.After preconditioning with Arglabin,the lung pathological injury in mice from the lung ischemia-reperfusion group was significantly reduced,the level of inflammation was reduced,IL-1β,MCP-1 and TNF-α,the level of pyroptosis was significantly inhibited,NLPR3 and ASC and the level of autophagy was significantly increased Beclin-1 and ATG7.Conclusion Arglabin may improve lung ischemia-reperfusion injury in mice by inhibiting pyroptosis and activating autophagy.

关 键 词：阿格拉宾 肺缺血再灌注 焦亡 自噬 

分 类 号：R73[医药卫生—肿瘤]