Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (INCOR), Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Eur J Cardiothorac Surg. 2023 Sep 7;64(3). doi: 10.1093/ejcts/ezad253.
Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17β-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17β-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation.
Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17β-oestradiol (280 µg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1β, IL-10 and tumour necrosis factor-α were quantified.
After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17β-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17β-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1β increased after I/R and 17β-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1β and IL-10 in lung explants, reduced by 17β-oestradiol.
Our results showed that 17β-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17β-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.
缺血再灌注引起的微血管功能障碍是各种外科手术中遇到的严重问题,导致全身炎症并影响到远处器官,特别是肺部。17β-雌二醇可减轻各种急性肺损伤形式的肺损伤反应。在这里,我们通过评估肺炎症来关注 17β-雌二醇在主动脉缺血再灌注(I/R)后的治疗效果。
24 只 Wistar 大鼠通过向胸主动脉内插入 2-F 导管进行 I/R,持续 20 分钟。再灌注持续 4 小时,再灌注 1 小时后给予 17β-雌二醇(280µg/kg,静脉注射)。假手术大鼠作为对照。进行支气管肺泡灌洗,并准备肺组织样本进行组织学分析和组织培养(培养物)。定量检测白细胞介素(IL)-1β、IL-10 和肿瘤坏死因子-α。
I/R 后,17β-雌二醇可减少支气管肺泡灌洗液中的白细胞数量。该治疗还减少了肺组织中的白细胞。I/R 增加了肺髓过氧化物酶的表达,而 17β-雌二醇则降低了其表达。I/R 后血清细胞因子诱导的中性粒细胞趋化因子 1 和 IL-1β增加,17β-雌二醇降低了细胞因子诱导的中性粒细胞趋化因子 1。I/R 增加了肺培养物中的 IL-1β和 IL-10,而 17β-雌二醇降低了它们的表达。
我们的结果表明,在再灌注期间给予 17β-雌二醇治疗可调节全身反应和主动脉夹闭后 I/R 对肺的影响。因此,我们可以认为 17β-雌二醇可能是一种辅助方法,可以减少手术中主动脉夹闭后肺恶化的风险。