摘要
目的研究三羟异黄酮预先给药对内毒素诱导大鼠急性肺损伤的保护作用及其机制。方法 32只雄性Wistar大鼠,随机分为4组,每组8只:对照组(C组)、三羟异黄酮组(G组)分别腹腔注射生理盐水1 ml／kg、三羟异黄酮50 mg／kg,30 min后,静脉注射生理盐水1 ml／kg;内毒素组(L组)、三羟异黄酮预预先给药组(Gpre组)分别腹腔注射生理盐水1 ml／kg、三羟异黄酮50 mg／kg,30 min后,静脉注射脂多糖6 mg／kg。注射脂多糖后4 h处死动物。测定支气管肺泡灌洗液(BALF)中蛋白浓度、髓过氧化物酶(MPO)活性及中性粒细胞(PMN)数。检测肺组织湿干重比(W／D)、丙二醛(MDA)含量、MPO 活性、肿瘤坏死因子-α(TNF-α)和血红素氧合酶-1(HO-1)mRNA、蛋白表达。观察肺组织病理学的改变。结果与C组比较,L组肺损伤严重、BALF中蛋白、MPO、PMN水平和肺组织W／D、MDA及MPO水平及TNF-α和HO-1 mRNA、蛋白表达水平升高(P<0．05或0．01),G组上述指标差异均无统计学意义(P >0．05);与L组比较,Gpre组除HO-1 mRNA、蛋白表达水平升高(P<0．05)外,其他指标均降低(P< 0．05或0．01)。结论三羟异黄酮预先给药对内毒素诱导大鼠急性肺损伤有一定的保护作用,与抑制PMN在肺组织的聚集、激活,TNF-α表达下调及HO-1表达上调有关。
Objective To investigate the effects ofgenistein 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 Ⅲ 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 30 min after IP NS 1 ml·kg^-1（ Ⅰ ） or genistein 50 mg·kg^-1 （ Ⅱ ）. In group Ⅲ and Ⅳ LPS 6 ml·kg^-1 was Ⅳ given 30 min after IP NS 1 ml·kg^-1 （ Ⅲ） 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-α mRNA, HO-1 mRNA, TNF-α, 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-α 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-α production, and a up-regulation in HO-1 expression.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2005年第11期820-823,共4页
Chinese Journal of Anesthesiology
