阿魏酸钠预处理在兔肺缺血再灌注损伤中保护作用和机制的实验研究

发布时间：2018-04-19 14:42

本文选题：缺血再灌注 + 阿魏酸钠　；参考：《苏州大学》2007年硕士论文

【摘要】： 目的通过制造在体兔肺缺血再灌注损伤(Lung Ischemic-reperfusion Injury LIRI)模型,观察中成药阿魏酸钠(sodium ferulate, SF)预处理对其的保护作用效果,并进一步探讨其保护作用的深层机制和原理。方法将18只成年新西兰大白兔不拘雌雄随机分为三组,每组6只,I/R组(行左肺缺血再灌注损伤),Sham组(假手术-只开胸而不行左肺缺血再灌注损伤),SF组(静脉给予SF 100mg/kg后再行左肺缺血再灌注损伤)。在呼吸机辅助下,开胸后左肺门阻断行缺血60分钟,开放左肺门再灌注120分钟作为缺血再灌注损伤模型。分别在缺血前,缺血60分钟,再灌注30分钟,在灌注120分钟抽取动脉血进行血清分离测定血清中SOD(超氧化物歧化酶),NO(一氧化氮);实验结束时摘取肺组织测肺组织湿/干重比值(W/D),制成组织匀浆测髓过氧化物酶(MPO),并留取肺组织在光镜下观察各实验组肺组织结构变化,观察肺组织损伤程度(LTD);以及图象分析系统观察各组肺组织细胞核核转录因子-Κb p65(NF κB p65)灰度值变化。结果经过60分钟缺血,120分钟的再灌注后,各实验组的检测指标呈现明显差异:与I/R组相比,SF组的病理组织学光镜下肺泡破坏减少,出血,炎症细胞浸润明显改善;肺损伤程度(LDT)与I/R组差异显著(P0.01),与S组无显著差异(P0.05);血清NO、SOD系统在SF组得到保护,破坏减少,与I/R组差异有统计学意义(PO.01),与S组差异不明显(P0.05);I/R组肺组织核转录因子-κB p65(NF κB p65)在细胞核,细胞浆表达较S组和SF组明显增加,呈现棕黄色,灰度值差异显著(P0.01) ,而S组和SF组无显著差异(P0.05).肺组织MPO在I/R组活力较余组明显增强(P0.01),而S组和SF组MPO活力相仿,无统计学意义(P0.05). 结论在体动物左肺阻断/开放是经典的肺脏缺血再灌注损伤模型,本实验亦证实其具有明确的实验损伤效果,在再灌注30分钟和2小时的损伤效果明显;中性粒细胞(PMN)在肺部的聚集和“扣押”,氧自由基(OFR)生成的增多和内源性NO的减少是肺再灌注损伤的重要因素,更重要的是NF κB p65的激活成为再灌注损伤焦点的恶性循环的扳机作用;阿魏酸钠对缺血再灌注损伤的保护效果是显而易见的,明显降低了肺脏的各项损伤指标(MPO,NF κB p65,)和增加了保护指标(NO,SOD);其机制可能是通过抑制PMN在肺中的聚集和NF κB p65的激活,保护了内源性NO,SOD免受破坏以及使得自由基的产生减少。
[Abstract]:Objective to investigate the protective effect of sodium ferulate (SF) preconditioning on lung Ischemic-reperfusion Injury LIRI model in rabbits, and to explore the mechanism and mechanism of its protective effect.Methods 18 adult New Zealand white rabbits were randomly divided into three groups.Six rats in each group were treated with left lung ischemia-reperfusion injury (sham group) (sham operation only left lung ischemia reperfusion injury without left lung ischemia reperfusion injury) SF group (after intravenous administration of SF 100mg/kg and then left lung ischemia reperfusion injury).After thoracotomy, the left hilar occlusion was performed for 60 minutes, and the left hilus was opened for 120 minutes as the model of ischemia-reperfusion injury.Before ischemia, 60 minutes of ischemia, 30 minutes of reperfusion,After 120 minutes of perfusion, arterial blood was extracted for serum separation and determination of serum SOD (superoxide dismutase (no)); lung tissue was removed at the end of the experiment to measure the wet / dry weight ratio of lung tissue and W / D, and tissue homogenate was made to measure myeloperoxidase (myeloperoxidase).The lung tissue of each experimental group was observed under light microscope.The degree of lung injury and the changes of nuclear transcription factor-kb p65(NF 魏 B p65 were observed by image analysis system.Results after 60 minutes of ischemia and 120 minutes of reperfusion, there were significant differences in the indexes of each experimental group: compared with the I / R group, the pathological histology of SF group decreased alveolar destruction, hemorrhage and inflammatory cell infiltration.The degree of lung injury (LDT) was significantly different from that of I / R group (P 0.01), but there was no significant difference between group S and group S (P 0.05), the serum NO-SOD system was protected and the damage was reduced in SF group.The expression of nuclear transcription factor-魏 B p65(NF 魏 B p65 in lung tissue in group I / R was significantly higher than that in group S and SF, and the expression of nuclear factor 魏 B p65(NF 魏 B p65 in lung tissue in group I / R was significantly higher than that in group S and SF (P 0.01).There was no significant difference between S group and SF group (P 0.05).The activity of MPO in group I / R was significantly higher than that in group I / R, but the activity of MPO in group S was similar to that in group SF, but there was no significant difference between group S and group SF (P 0.05).Conclusion the left lung occlusion / opening in vivo is a classical model of lung ischemia-reperfusion injury. This experiment also confirmed that it has a clear experimental injury effect, and the injury effect is obvious at 30 minutes and 2 hours of reperfusion.The accumulation and sequestration of neutrophil PMN in the lung, the increase of oxygen free radical (OFRR) production and the decrease of endogenous no are important factors of lung reperfusion injury.More importantly, the activation of NF 魏 B p65 acts as the trigger for the vicious cycle of reperfusion injury, and the protective effect of sodium ferulate on ischemia-reperfusion injury is obvious.The mechanism may be that by inhibiting the accumulation of PMN in the lung and the activation of NF 魏 B p65, the endogenous No-SOD is protected from destruction and the production of free radicals is reduced by inhibiting the accumulation of PMN in the lung and the activation of NF 魏 B p65.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R363

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