Sezen Şaban Cem, Kucuk Aysegul, Özer Abdullah, Kılıç Yiğit, Mardin Barış, Alkan Metin, Erkent Fatmanur Duruk, Arslan Mustafa, Ünal Yusuf, Oktar Gürsel Levent, Tosun Murat
Department of Histology and Embryology, Kirikkale University Medical Faculty, Kirikkale, Turkey.
Department of Physiology, Dumlupinar University Medical Faculty, Kutahya, Turkey.
Drug Des Devel Ther. 2018 May 22;12:1347-1352. doi: 10.2147/DDDT.S160092. eCollection 2018.
The aim of this study was to investigate the effects of levosimendan and thymoquinone (TQ) on lung injury after myocardial ischemia/reperfusion (I/R).
Twenty-four Wistar albino rats were included in the study. The animals were randomly assigned to 1 of 4 experimental groups. In Group C (control group), left anterior descending artery was not occluded or reperfused. Myocardial I/R was induced by ligation of the left anterior descending artery for 30 min, followed by 2 h of reperfusion in the I/R, I/R-levosimendan (24 µg/kg) (IRL) group, and I/R-thymoquinone (0.2 mL/kg) (IRTQ) group. Tissue samples taken from the lungs of rats were histochemically stained with H&E and immunohistochemically stained with p53, Bcl 2, Bax, and caspase 3 primer antibodies.
Increased expression of p53 and Bax was observed (4+), especially in the I/R group. In IRTQ and IRL groups, expression was also observed at various locations (2+, 3+). H&E staining revealed that that the lungs were severely damaged and the walls of the alveoli were too thick, the number of areas examined was increased during the evaluation. Caspase 3 expression was observed to be at an (1+, 2+) intensity that was usually weak and diffuse in multiple areas. Bcl 2 was not found to be expressed in any of the tissues. H&E staining revealed that that the lungs were severely damaged in the I/R group, with the walls of the channels and alveoli thickened and edematous, and also an intense inflammatory cell migration was observed. Immunohistochemical staining was more prominent in inflammatory areas and structures around the terminal bronchioles.
The findings in our study have shown that administration of levosimendan and TQ during I/R increases expression of caspase 3, p53, and Bax in lung tissue and has a protective effect on lung as distant organ. We suggest that findings of this study be elucidated with further large-scale clinical studies.
本研究旨在探讨左西孟旦和百里醌（TQ）对心肌缺血/再灌注（I/R）后肺损伤的影响。
本研究纳入24只Wistar白化大鼠。将动物随机分为4个实验组中的1组。在C组（对照组）中，左前降支动脉未闭塞或再灌注。在I/R组、I/R-左西孟旦（24μg/kg）（IRL）组和I/R-百里醌（0.2mL/kg）（IRTQ）组中，通过结扎左前降支动脉30分钟，然后再灌注2小时诱导心肌I/R。从大鼠肺部采集的组织样本用苏木精和伊红（H&E）进行组织化学染色，并用p53、Bcl-2、Bax和半胱天冬酶3引物抗体进行免疫组织化学染色。
观察到p53和Bax的表达增加（4+），尤其是在I/R组。在IRTQ组和IRL组中，在不同位置也观察到表达（2+，3+）。H&E染色显示肺严重受损，肺泡壁增厚，在评估过程中检查的区域数量增加。观察到半胱天冬酶3的表达强度为（1+，2+），通常在多个区域较弱且弥漫。未发现Bcl-2在任何组织中表达。H&E染色显示I/R组肺严重受损，通道和肺泡壁增厚且水肿，还观察到强烈的炎性细胞迁移。免疫组织化学染色在终末细支气管周围的炎症区域和结构中更明显。
我们研究中的发现表明，在I/R期间给予左西孟旦和TQ可增加肺组织中半胱天冬酶3、p53和Bax的表达，并对作为远处器官的肺具有保护作用。我们建议通过进一步的大规模临床研究来阐明本研究的结果。
