Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury
Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury
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DOI：
10.1183/09031936.00052408
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发表时间：
2009-03-01
影响因子：
24.3
通讯作者：
Rocco, P. R. M.
中科院分区：
文献类型：
--
作者：
Silva, P. L.;Garcia, C. S. N. B.;Rocco, P. R. M.
本研究比较了早期短期和长期低剂量皮质类固醇治疗急性肺损伤（ALI）的效果。120只BALB/c小鼠随机分为5组。对照组采用气管内滴注生理盐水。在ALI组，小鼠接受大肠杆菌脂多糖（10 μ g / t）。ALI动物进一步随机分为4个亚组，分别在6小时、24小时或每天（共7天，从第1天开始）接受生理盐水（0.1 mL静脉注射）或甲基强的松龙（2 mg中心点kg（-1）静脉注射）。1、3和8周时，测定大鼠体内和体外肺力学和组织学（光镜和电镜）、胶原和弹性纤维含量、支气管肺泡灌洗液中细胞因子及基质金属蛋白酶(MMP)-9和-2的表达。体内（静弹性和粘弹性压力）和体外（组织弹性和阻力）肺力学、肺泡塌陷、细胞浸润、胶原和弹性纤维含量以及MMP-9和MMP-2的表达均在1周时升高。甲基强的松龙可以完全解决肺力学问题，避免纤维弹性形成，并增加独立于类固醇治疗设计的MMP-9和MMP-2的表达。因此，早期短期低剂量甲基强的松龙与长期治疗急性肺损伤同样有效。
The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI).In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally (i.t.) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 mu g i.t.). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v.) or methylprednisolone (2 mg center dot kg(-1) i.v.) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured.In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design.Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.