Demiröz Şevki Mustafa, Küçük Ayşegül, Tekin Esra, Söylemez Sibel, Yılmaz Hanife, Sezen Şaban Cem, Atlı Muharrem, Demirtaş Hüseyin, Özer Abdullah, Ünal Yusuf, Arslan Mustafa
Department of Thoracic Surgery, Faculty of Medicine, Gazi University, Ankara 06510, Turkey.
Department of Physiology, Faculty of Medicine, Kutahya Health Sciences University, Kutahya 43000, Turkey.
Medicina (Kaunas). 2025 Jul 18;61(7):1298. doi: 10.3390/medicina61071298.
: This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, in a rat model of lung ischemia-reperfusion (I/R) injury, with a focus on myocardial tissue involvement. : Twenty-four male Wistar rats were randomly assigned to four groups: sham, bosentan, I/R, and I/R + bosentan. Lung I/R injury was induced by hilar clamping for 45 min, followed by 60 min of reperfusion. Bosentan (30 mg/kg) was administered intraperitoneally 30 min prior to the procedure. Myocardial tissue was evaluated histopathologically for structural disorganization, inflammation, fibrosis, and edema. TGF-β1 protein levels in myocardial tissue were compared across the groups using β-actin as the loading control. ELISA was used to quantify ET-1, NF-κB, and p53 levels, while spectrophotometric analysis was employed to assess MDA levels and the activities of SOD and CAT enzymes in heart tissue. : The I/R group exhibited significant myocardial disorganization, inflammation, and interstitial edema compared to the sham and bosentan groups. Bosentan treatment markedly ameliorated these histopathological alterations. Additionally, the I/R group showed elevated levels of ET-1, NF-κB, p53, and MDA, along with reduced SOD and CAT activities; these changes were significantly attenuated by bosentan administration. Bosentan treatment significantly reduced myocardial ET-1 levels (from 136.88 ± 5.02 to 120.18 ± 2.67 nmol/g, = 0.003), NF-κB levels (from 0.87 ± 0.04 to 0.51 ± 0.03 ng/mg, = 0.002), and TGF-β1 expression (from 1.72 ± 0.10 to 0.91 ± 0.08 relative units, = 0.001). Moreover, bosentan increased antioxidant enzyme activities, elevating SOD levels from 21.45 ± 1.23 to 32.67 ± 1.45 U/mg protein ( = 0.001) and CAT levels from 15.22 ± 0.98 to 25.36 ± 1.12 U/mg protein ( = 0.002). : Bosentan exerts cardioprotective effects in rats subjected to lung I/R injury by reducing myocardial damage, inflammation, and oxidative stress. These findings suggest that bosentan may serve as a potential therapeutic agent for preventing remote organ injury associated with pulmonary I/R.
本研究旨在探讨内皮素受体拮抗剂波生坦在大鼠肺缺血再灌注（I/R）损伤模型中的心脏保护作用，重点关注心肌组织受累情况。24只雄性Wistar大鼠随机分为四组：假手术组、波生坦组、I/R组和I/R + 波生坦组。通过夹闭肺门45分钟诱导肺I/R损伤，随后再灌注60分钟。在手术前30分钟腹腔注射波生坦（30 mg/kg）。对心肌组织进行组织病理学评估，观察结构紊乱、炎症、纤维化和水肿情况。以β-肌动蛋白作为内参，比较各组心肌组织中转化生长因子-β1（TGF-β1）蛋白水平。采用酶联免疫吸附测定（ELISA）法测定内皮素-1（ET-1）、核因子-κB（NF-κB）和p53水平，同时采用分光光度法分析心脏组织中丙二醛（MDA）水平以及超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性。与假手术组和波生坦组相比，I/R组心肌出现明显的结构紊乱、炎症和间质水肿。波生坦治疗显著改善了这些组织病理学改变。此外，I/R组ET-1、NF-κB、p53和MDA水平升高，SOD和CAT活性降低；波生坦给药可显著减轻这些变化。波生坦治疗显著降低心肌ET-1水平（从136.88 ± 5.02降至120.18 ± 2.67 nmol/g，P = 0.003）、NF-κB水平（从0.87 ± 0.04降至0.51 ± 0.03 ng/mg，P = 0.002）和TGF-β1表达（从1.72 ± 0.10降至相对单位0.91 ± 0.08，P = 0.001）。此外，波生坦提高了抗氧化酶活性，使SOD水平从21.45 ± 1.23升高至32.67 ± 1.45 U/mg蛋白（P = 0.001），CAT水平从15.22 ± 0.98升高至25.36 ± 1.12 U/mg蛋白（P = 0.002）。波生坦通过减轻心肌损伤、炎症和氧化应激，对遭受肺I/R损伤的大鼠发挥心脏保护作用。这些研究结果表明，波生坦可能是预防与肺I/R相关远程器官损伤的潜在治疗药物。
