不同剂量氢化可的松对急性肺损伤大鼠多形核白细胞氧自由基释放的影响

Primary study on the effects of different dosage of hydrocortisone on the release of oxygen free radicals from polymorphonuclear neutrophils in rats with acute lung injury induced by lipopolysaccharide

目的观察不同剂量氢化可的松(HC)对内毒素(LPS)致鼠急性肺损伤(ALI)病理及多形核白细胞(PMN)释放氧自由基(OFR)的影响,并探讨其原因。方法大鼠腹腔注射O111B4,2000亿/kg复制ALI模型。40只大鼠随机分为空白组、内毒素组(LPS组)、大剂量HC组(150mg/kg)、中剂量HC组(20mg/kg)、小剂量HC组(6mg/kg),注药6h后采集标本,观察各组大鼠肺湿/干比(W/D值)、肺通透性指数(PPI)、肺病理变化(光镜、电镜)等指标,并检测PMN释放的OFR水平,在不同组之间进行比较。结果W/D值、PPI及肺光镜病理半定量评分等指标,LPS组均显著高于空白组(P<0.05)。使用HC干预后,小剂量HC组较LPS组各项指标均显著降低(P<0.05),中剂量HC组仅肺病理半定量评分较LPS组降低,差异有显著性(P<0.05),大剂量HC组各项指标与LPS组比较,差异均无显著性。OFR释放水平,LPS组显著高于空白组(P<0.01),应用HC后,各剂量组均显著降低(P<0.05),但不同剂量HC组差异无显著性。结论LPS组大鼠OFR产生明显增多,提示其在ALI发病中起重要作用;不同剂量激素均可对ALI大鼠OFR释放产生明显抑制,其抑制作用与激素剂量无关;小剂量激素组对ALI大鼠肺病理损伤的改善最明显,中剂量组次之,大剂量组无明显改善作用。

Objective To investigate the effects of different dosage of hydrocortisone(HC)on re-lease of oxygen free radicals(OFR)from polymorphonuclear neutrophils(PMN)in rats with acute lung injury(ALI)induced by lipopolysaccharide(LPS),and elucidate its possible mechanism.Methods A rat model of ALI was established by peritoneal injection of2×1011Escherichia coli/kg.Forty rats were divided into five groups:normal control group,LPS group,high dose HC group(150mg/kg),medium dose HC group(20mg/kg)and low dose HC group(6mg/kg).Samples were collected after6hours of HC or normal saline injection.Histopathological changes were examined;indexes of lung injury(wet/dry ratio,total protein concentration in bronchoalveolar lavage fluid)and index of lung permeability were measured.The level of OFR released by PMN was measured by chemiluminescence method.The differences in these five groups mentioned above were compared.Results The values of W/D,index of lung permeability and semi-quantitative scores of histopathological changes in LPS group were significantly higher than those in normal control group(P<0.05).After injection of HC,the values in low dose group were significantly lower than those in LPS group(P<0.05).In medium dose group,only the score of pathological changes was significant lower than that in LPS groups(P<0.05).With no significant differences between the high HC dose group and LPS group(P>0.05).The level of OFR released by PMN in LPS group was statistical higher than that in normal control group(P<0.05).After injection of HC,levels of OFR released by PMN in three HC groups were significantly lower than that in LPS group(P<0.05).However,there were no significant differences among three HC groups in levels of OFR(P>0.05).Conclusions OFR may play an important role in acute lung injury.Hydrocortisone can inhibit the release of oxygen free radicals from polymorphonuclear neutrophils, this inhibition has no dose-dependent effect.