自噬相关蛋白Beclin-1在大鼠肺移植供肺缺血再灌注损伤中的表达及意义探究

发布时间：2018-05-30 11:04

本文选题：肺移植 + 自噬　；参考：《南昌大学》2015年硕士论文

【摘要】：目的:建立大鼠原位异体肺移植模型,明确自噬相关蛋白Beclin-1在大鼠肺移植供肺缺血再灌注损伤中的表达,然后通过调控自噬,研究Beclin-1蛋白表达含量、细胞凋亡水平及肺功能指标的变化,揭示自噬作用对肺移植供肺I/R损伤及肺功能指标的影响。方法:建立大鼠原位左肺移植模型,分别于供肺灌注、冷缺血保存、移植后再灌注2小时、6小时、12小时获取供肺标本;检测供肺Beclin-1蛋白的表达、细胞凋亡及肺功能指标水平。通过调控自噬,分别用LPD液、3-MA+LPD液、雷帕霉素+LPD液灌注、冷缺血保存供肺6小时后行肺移植术,于前一部分得出的自噬水平峰值时间点再灌后获取供肺,再次检测供肺Beclin-1蛋白的表达、细胞凋亡及肺功能指标水平。结果:1、建立了稳定的大鼠原位肺移植模型。2、Beclin-1蛋白的表达在供肺缺血后逐渐上升,在再灌注6h达到高峰,供肺组织细胞凋亡水平及肺功能损伤指标在SD大鼠供肺灌注、冷缺血、再灌注后6h所获取的肺标本中达到峰值。3、在3-MA+LPD液组Beclin-1蛋白的表达及细胞凋亡水平明显降低,肺功能损伤减轻。雷帕霉素+LPD液组Beclin-1蛋白的表达及细胞凋亡水平明显升高,肺功能损伤加重。结论:1、肺移植供肺缺血再灌注后,自噬相关蛋白Beclin-1及细胞凋亡水平升高,并在术后6h达到高峰。2、通过抑制自噬,自噬相关蛋白Beclin-1表达降低,细胞凋亡水平减轻,减轻肺功能损伤。抑制自噬对肺移植缺血再灌注损伤具有保护作用。3、通过激活自噬,自噬相关蛋白Beclin-1表达升高,细胞凋亡水平加重,加重肺功能损伤。激活自噬对肺移植缺血再灌注损伤具有促进作用。4、自噬在大鼠肺移植缺血再灌注损伤中可能起到了促进作用。
[Abstract]:Objective: to establish a rat model of orthotopic lung transplantation and to investigate the expression of autophagy associated protein (Beclin-1) in ischemia-reperfusion injury of donor lung in rats, and then to study the expression of Beclin-1 protein by regulating autophagy. The changes of apoptosis level and lung function index revealed the effect of autophagy on I / R injury and lung function index of donor lung transplantation. Methods: the model of orthotopic left lung transplantation was established in rats. Donor lung samples were obtained from donor lung perfusion, cold ischemia preservation and reperfusion for 2 hours, 6 hours and 12 hours, respectively, and the expression of Beclin-1 protein, apoptosis and lung function index were detected. By regulating autophagy, the donor lung was obtained after lung transplantation after 6 hours of cold ischemia preservation with LPD solution 3-MA LPD solution and rapamycin LPD solution, and the donor lung was obtained after reperfusion at the peak time point of autophagy level obtained in the first part of the experiment. The expression of Beclin-1 protein, apoptosis and lung function were detected again. Results the stable rat model of orthotopic lung transplantation was established. The expression of Beclin-1 protein increased gradually after ischemia of donor lung and reached its peak at 6 h after reperfusion. The level of apoptosis of donor lung tissue and the index of lung function injury were perfused into donor lung and cold ischemia in SD rats. The lung samples obtained 6 hours after reperfusion reached the peak value of .3. the expression of Beclin-1 protein and the level of apoptosis in the 3-MA LPD fluid group were significantly decreased, and the lung function injury was alleviated. In rapamycin LPD solution group, the expression of Beclin-1 protein and the level of apoptosis were significantly increased, and the lung function injury was aggravated. Conclusion the levels of autophagy associated protein (Beclin-1) and apoptosis in lung grafts increased after ischemia reperfusion and reached a peak at 6 h after lung transplantation. By inhibiting autophagy, the expression of autophagy associated protein Beclin-1 decreased and the level of apoptosis decreased. Reduce lung function injury. Inhibition of autophagy has a protective effect on ischemia-reperfusion injury of lung transplantation. By activating autophagy, the expression of autophagy associated protein Beclin-1 is increased, the level of apoptosis is aggravated, and the injury of lung function is aggravated. Activation of autophagy can promote ischemia-reperfusion injury of lung transplantation. 4. Autophagy may play a role in promoting ischemia-reperfusion injury of lung transplantation in rats.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R655.3

【参考文献】