rAAV9介导HIF-1α对糖尿病小鼠缺血后处理的影响  

Effects of rAAV9-HIF-1α on Ischemic Postconditioning in Diabetic Mice

作　　者：李佳馨 李鑫[1] 吴建江[1] 陈思宇[1] 王江[1] Li Jiaxin;Li Xin;Wu Jianjiang(The First Affiliated Hospital of Xinjiang Medical University,Xinjiang 830054,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,乌鲁木齐830054

出　　处：《医学研究杂志》2020年第8期38-41,66,共5页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81960053)。

摘　　要：目的观察缺血后处理对糖尿病小鼠心肌缺血/再灌注致急性肺损伤的保护作用,探讨rAAV9-HIF-1α对缺血后处理作用的影响机制,方法选择雄性db/db小鼠40只,按照随机数字表法分为假手术组(S组)、心肌缺血/再灌注组(I/R组)、缺血后处理组(IPostC组)、rAAV9-HIF-1α+缺血后处理组(HIPostC组)。采用尾静脉注射法注射rAAV9-HIF-1α;结扎冠状动脉左前降支建立心肌缺血/再灌注模型;于再灌注15min前灌注5min、缺血5min连续3个循环建立缺血后处理模型。心内取血后处死小鼠.取肺组织,HE染色观察病理学变化;CBA流式法检测炎性细胞因子(IL-6、TNF-α及IL-10);试剂盒检测氧化应激相关因子(MDA.SOD);Western blot法检测低氧诱导因子HlF-1α。结果与S组比较,1/R组的肺组织损伤严重,氧自由基和炎性细胞因子含量明显升高;与I/R组比较,IPostC组氧自由基含量降低,但促炎性细胞因子仍大量存在,而HIPostC组的炎性细胞因子和氧自由基含量均显著降低,HIF-1α的含量显著升高。结论糖尿病心肌缺血/再灌注损伤时炎性细胞因子释放、氧化应激激活以及HIF信号通路损伤直接导致急性肺损伤,rAAV9-HIF-1α可调控缺血后处理通过上述机制在一定程度上减轻肺损伤,发挥围术期肺保护作用。Objective To observe the protective effeet of ischemic postconditioning on acute lung injury by myocardial ischemia/reperfusion in diabetes mellius.To investigate the effect of rAAV9-HIF-1 on ischemic postonditioning.Methods Forty male db/db mice were selected and divided into Sham operation group(S group),ischemia/reperfusion group(I/R group),ischemie postconditioning group(IPostC group)and rAAV9-HIF-1α+ischemic postconditioning group(HIPostC group)according to the random number ta-ble method.rAAV9-HIF-I was injected by tail vein.Myocardial isc hemia/reperfusion model was established by ligating the left anterior descending coronary artery.The model of ischemie postconditioning was established by 3 consecutive cyeles of 5 minutes reperfusion and 5 minutes ischemia before 15minutes reperfusion.The lung issues were taken.The pathological changes were observed by HE staining.The inf1αrmatory factors(IL-6,IL-10 and TNF-α)was detected by CBA flow cytometry.Oxidative stress-re1αted factors(MDA,SOD)were dected by detection kit.Hypoxia inducible factor(HIF-1a)was detected by Western blot.Results Compared with the s group,the lung tssues of the I/R group were more serious with a 1αrge number of pro-infammatory factors and reactive oxygen species.Compared with the 1/R group,the content of oxygen free radicals in the IPostC group was reduced,but the content of in1αmmatory factors was still in 1αrge quantities,while the lung injury in the HIPostC group was mild with significant decrease in inf1αmmatory factors and reactive oxygen species,and significant increase in HIF-1α content.Conclusion Acute lung injury is direetly eaused by the release of inf1αmmatory factors,oxidative stress activation and HIF signaling pathway injury in diabetic myocardial ischemia/'reperfusion injury.The injection of rAAV9-HIF-1a by the tail vein can regu1αte the ischemic postconditioning,which can reduce the lung injury and p1αy the perioperative lung protection role.

关 键 词：再灌注损伤急性肺损伤 缺血后处理低 氧诱导因子-1α 

分 类 号：R614[医药卫生—麻醉学]