雷帕霉素预处理对大鼠肢体缺血-再灌注肺损伤的影响  

Effect of Rapamycin Pretreatment on Lung Injury Induced by Limb Ischemia-Reperfusion in Rats

作　　者：袁志军 唐斌 罗振中[2] 黄丹[2] 

机构地区：[1]江西省分宜县中医院,江西新余336600 [2]南昌大学第二附属医院,江西南昌336600

出　　处：《中国药业》2017年第21期7-9,共3页China Pharmaceuticals

基　　金：江西省卫生计生委科技计划项目[20165283]

摘　　要：目的探讨雷帕霉素预处理对大鼠肢体缺血-再灌注肺损伤的影响,为临床应用及预防提供理论参考。方法将60只健康雄性SD大鼠采用随机数字表法均分为对照组(C组)、肢体缺血-再灌注组(I/R组)、雷帕霉素预处理组(R组)3组,各20只。所有动物缺血前12 h禁食,自由饮水,麻醉后固定于操作台,于右侧腹股沟处切开皮肤,暴露股动脉、股静脉和股神经;C组仅分离股动脉、股静脉和股神经;I/R组和R组用无创血管夹于接近腹股沟韧带处夹闭股动脉,迫使大鼠双后肢缺血2 h,后取去血管夹使得再灌注3 h;R组于下肢缺血前灌胃雷帕霉素。应用超声血流仪监测血流,以未监测到血液流动为缺血,监测到血液流动为再灌注的指标;再灌注3 h后处死大鼠,心脏取血2 mL,离心取血清,硫代巴比妥法测定丙二醛(MDA)的浓度,酶联免疫吸附(ELISA)法检测白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)的浓度;取肺组织计算干湿比及行免疫组化观察肺组织病理学结果。结果与C组比较,I/R组肺W/D、血清MDA,IL-1β,IL-6和TNF-α水平均明显升高(P<0.01),与I/R组比较,R组肺W/D,血清MDA,IL-1β,IL-6和TNF-α水平均明显降低(P<0.05);光镜下C组大鼠的肺组织纹理结构尚完整,肺泡间隔均匀一致,见少量炎性细胞浸润,肺泡腔清楚可见;I/R组大鼠肺泡上皮细胞增生,肺间质明显增生,肺泡壁增厚,可见大量的炎性细胞浸润,毛细血管明显扩张充血,肺泡壁及肺泡间质中可见大量中性粒细胞;R组大鼠肺组织病理改变较I/R组明显减轻,炎性细胞浸润明显减少,仅有少量红细胞渗出。结论雷帕霉素预处理可减轻肢体缺血-再灌注诱发肺损伤,其机制可能与抗氧化应激和抗炎反应有关。Objective To investigate the effect of rapamycin pretreatment on lung injury induced by limb ischemia-reperfusion in rats, to provide theoretical basis for clinical application and its prevention and treatment of lung injury induced by limb ischemia-reperfusion. Methods Totally 60 healthy male SD rats were divided into control group（ group C）,limb ischemia reperfusion group（ group I/R）,rapamycin pretreatment group（group R） by random number table method,20 cases in each group. 12 h before ischemia,all were fasted,free drinking water and fixed on the operating table after anesthesia. In the right groin skin incision,the exposed femoral artery,femoral vein and femoral nerve. Only femoral artery,femoral vein and femoral nerve separated in group C,the femoral artery was clamped at the proximal inguinal ligament with a noninvasive vascular clamp in group I/R and group R,in order to force the hind limb of the rats to undergo ischemia for 2 h,and the vascular clamp was removed to make the reperfusion for 3 h. In group R,rapamycin was injected into the lower limb before ischemia. TTFM was used to monitor blood flow,no blood flow was monitored for ischemia,and blood flow was monitored as an indicator of reperfusion. After reperfusion for 3 h,the rats were sacrificed,and 2 mL blood was taken from the heart,the blood serum was taken by centrifuging. The concentration of MDA was determined by thiobarbituric acid method,and the levels of IL-1β,IL-6 and TNF-α were detected by ELISA. The lung tissue was taken,and the pathological results of lung tissue were observed by calculating the ratio of dry-wet and immunohistochemistry. Results Compared with group C,theconcentration of W/D in lung,serum MDA,IL-1β,IL-6 and TNF-α in group I/R increased significantly（ P〈0. 01）. Compared with I/R group,the concentration of W/D in lung,serum MDA,IL-1β,IL-6 and TNF-α in group R decreased significantly（ P〈0. 05）. Under light microscope,the structure of lung tissue in group C was intact,and the alveolar septa were un

关 键 词：雷帕霉素 肢体缺血-再灌注 肺损伤 

分 类 号：R965.2[医药卫生—药理学] R978.1[医药卫生—药学]