前列地尔注射液通过抑制自噬减轻肺缺血再灌注损伤

发布时间：2018-05-06 21:03

本文选题：肺缺血再灌注损伤 + 前列地尔注射液　；参考：《山西医科大学》2017年硕士论文

【摘要】：目的:探讨大鼠肺组织缺血再灌注损伤时自噬水平的变化以及肺缺血再灌注损伤时前列地尔注射液的保护作用,进一步研究前列地尔注射液能否通过调节自噬减轻大鼠肺的缺血再灌注损伤(ischemia and reperfusion injury,IRI)。方法:健康成年雄性Wistar大鼠75只,采用开胸夹闭右肺门建立IRI模型,将75只Wistar大鼠编号后按随机数字表法分为五组,分别为:对照组(Sham组)、缺血再灌注处理组(I/R组)、前列地尔注射液处理组(Alp组)、前列地尔注射液+自噬激活剂雷帕霉素(Rapamycin)处理组(Alp+Rap组)和Rapamycin处理组(Rap组),各15只。缺血60min,再灌注120min后处死大鼠。再灌注结束后经胸主动脉取动脉血测定动脉血氧饱和度(PaO2);大鼠处死后取部分右肺,称湿重、干重,计算湿干重比(W/D),石蜡包埋剩余肺组织,并切片,苏木精-伊红(HE)染色后电镜观察肺组织病理变化,计算其肺损伤病理学评分;另免疫荧光双染色法观察自噬相关蛋白LC3、Beclin-1的染色情况。结果:与Sham组相比,I/R组PaO2明显降低,W/D值明显增大,肺损伤程度明显加重,LC3、Beclin-1蛋白表达水平明显上升(P㩳0.05)。与I/R组比较,Alp组PaO2值显著增大,W/D值显著减小,肺组织损伤程度显著减轻,LC3、Beclin-1蛋白表达水平明显下降(P㩳0.05)。Rapamycin能削弱前列地尔注射液的作用。结论:肺缺血再灌注损伤时自噬水平升高,前列地尔注射液可减轻大鼠肺组织肺缺血再灌注损伤,且与自噬有关,激活自噬则可以加重肺的缺血再灌注损伤。
[Abstract]:Objective: to investigate the changes of autophagy level in lung tissue of rats with ischemia-reperfusion injury and the protective effect of alprostadil injection on lung ischemia-reperfusion injury. To further study whether alprostadil injection can alleviate and reperfusion injury by regulating autophagy in rats. Methods: 75 healthy adult male Wistar rats were used to establish IRI model by opening the right lung hilum. The 75 Wistar rats were numbered and randomly divided into five groups. The results were as follows: control group (Sham group), ischemia-reperfusion group (I / R group), alprostadil injection group (Alp group), alprostadil injection autophagy activator rapamycin (rapamycin) treatment group (Alp Rap group) and Rapamycin treatment group (Rap group, 15 rats each). Rats were killed after ischemia for 60 minutes and reperfusion for 120min. After reperfusion, arterial blood was taken from the thoracic aorta to determine the arterial oxygen saturation. After the rats were killed, part of the right lung was taken to weigh wet weight and dry weight, the wet / dry weight ratio was calculated, and the remaining lung tissue was embedded in paraffin and sectioned. The pathological changes of lung tissue were observed by electron microscope after hematoxylin and eosin HEV staining, and the pathological scores of lung injury were calculated, and the staining of autophagy associated protein LC3 / Beclin-1 was observed by double immunofluorescence staining. Results: compared with the Sham group, the PaO2 decreased significantly in the I / R group and the W / D value increased significantly, and the expression level of Beclin-1 protein increased significantly in the lung injury group (P < 0.05). Compared with the I / R group, the PaO2 value of Alp group increased significantly and the W / D value decreased significantly, and the degree of lung injury significantly reduced the expression level of LC3 / Beclin-1 protein. Rapamycin could weaken the effect of proprostadil injection. Conclusion: the level of autophagy increased during lung ischemia-reperfusion injury. Alprostadil injection can attenuate lung ischemia-reperfusion injury in rats and is related to autophagy. Activation of autophagy can aggravate the ischemia-reperfusion injury of lung.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R563

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