Protective effect of genistein pretreatment against endotoxin-induced acute lung injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of genistein pretreatment on endotoxin-induced acute lung injury in rats and assess the possible mechanism. Methods Thirty-two male Wistar rats weighing 240-280 g were randomly divided into 4 groups ( n = 8, each group) group Ⅰ control; group Ⅱ genistein; group ? LPS and group Ⅳ genistein pretreatment. The jugular vein was cannulated for administration of fluid and drug. The animals were anesthetized with intraperitoneal 3% pentobarbital 40 mg? kg-1 . In group Ⅰ and Ⅱ Ⅳ normal saline (NS) 1 ml?kg-1 was Ⅳ given 30min after IP NS 1 ml?kg-1 (Ⅰ ) or genistein 50 mg?kg-1 (Ⅱ ). In group ? and Ⅳ LPS 6 ml? kg-1 was Ⅳ given 30 min after IP NS 1 ml?kg-1 (?) or genistein 50 mg? kg -1 (Ⅳ). Four hours after.LPS injection, rats were sacrificed. The lungs were removed for evaluation of histological injury and determination of wet/dry lung weight (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, expression of TNF-f55 mRNA, HO-1 mRNA, TNF-f55, and HO-1. Bronchoalveolar lavage fluid (BALF) was collected for determination of PMN count, protein content, and MPO activity.Results LPS administration induced marked lung injury and significant increases in W/D ratio, MPO activity, and MDA content in the lung tissues, and PMN count, protein content, and MPO activity in BALF. All of these changes were significantly reduced by genistein pretreatment. Genistein also markedly suppressed LPS-induced expression of TNF-a mRNA and protein, and enhanced LPS-induced expression of HO-1 mRNA and protein. Conclusion Pretreatment with genistein has protective effect against endotoxin-induced acute lung injury. The underlying mechanism is via an inhibition of neutrophilic recruitment and activity, a down-regulation in TNF-f55 production, and a up-regulation in HO-1 expression.