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左肺切除后甲基强的松龙对剩余肺血管周围水肿、炎症浸润、VEGF 和 TGF-β免疫表达的影响。

Effect of methylprednisolone on perivascular pulmonary edema, inflammatory infiltrate, VEGF and TGF-beta immunoexpression in the remaining lungs of rats after left pneumonectomy.

机构信息

Departamento de Cardiopneumologia, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Brasil.

出版信息

Braz J Med Biol Res. 2011 Jul;44(7):647-51. doi: 10.1590/s0100-879x2011007500061. Epub 2011 May 13.

DOI:10.1590/s0100-879x2011007500061
PMID:21584441
Abstract

Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO(2)/FiO(2) ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO(2)/FiO(2) ratio, neutrophil density or TGF-β expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-β expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation.

摘要

肺切除术与高发病率和死亡率相关,其中术后肺水肿是主要原因之一。手术后继发的固有炎症过程在其病理生理学中已有研究。糖皮质激素的应用与预防这种水肿有关,但没有实验数据支持这一假说。我们评估了甲泼尼龙对接受左肺切除术的大鼠剩余肺脏的影响,以评估其对水肿和炎症标志物的影响。40 只雄性 Wistar 大鼠,体重 300 克,行左肺切除术,并随机分为接受皮质类固醇治疗组和不治疗组。术前给予甲泼尼龙 10mg/kg。恢复后,动物在 48 和 72 小时时处死,测定 pO(2)/FiO(2)比值。通过血管周围面积与血管面积之比测量右肺血管周围水肿,并通过手动计数测量中性粒细胞密度。通过免疫组化光镜评估血管内皮生长因子(VEGF)和转化生长因子-β(TGF-β)的组织表达。两组动物在 72 小时时均出现血管周围水肿(P = 0.0031)。接受皮质类固醇治疗的手术动物与未接受皮质类固醇治疗的动物在 pO(2)/FiO(2)比值、中性粒细胞密度或 TGF-β表达方面无差异。术后 48 和 72 小时,接受甲泼尼龙治疗的动物的 VEGF 组织表达升高(P = 0.0243)。甲泼尼龙不能增强气体交换,也不能避免炎症浸润,TGF-β表达也表明炎症过程与肺水肿的形成无关。然而,该组 VEGF 的过度表达表明,甲泼尼龙与 VEGF 的升高有关。

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