不同剂量胆红素对内毒素致大鼠急性肺损伤的保护作用

The protective effects of bilirubin with different doses against LPS-induced acute lung injury in rats

目的 探讨不同剂量的胆红素对内毒素致急性肺损伤（ALI）的保护作用及其可能机制。方法将雄性Wistar大鼠（200-250 g）40只,按随机数字表法分为正常对照组、ALI动物模型组、大剂量胆红素干预组和小剂量胆红素干预组。观察肺组织形态学变化,检测肺组织肺系数（LI）、支气管肺泡灌洗液（BALF）中白细胞（WBC）计数和中性粒细胞（PMN）百分比、蛋白质含量（Pr）、肺泡通透指数（LPI）;测定肺组织匀浆中超氧化物歧化酶（SOD）、脂质过氧化产物丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）含量变化。结果 ①ALI模型组LI、BALF中WBC计数、PMN百分比和Pr及LPI均显著高于生理盐水对照组（P均〈0.01）。大剂量胆红素干预组LI,BALF中WBC计数和LPI均显著低于ALI模型组（P均〈0.01）,PMN百分比和Pr也明显低于ALI模型组（P均〈0.05）,且与生理盐水对照组差异无统计学意义。小剂量胆红素组LI、BALF中PMN百分比、Pr和LPI均显著低于ALI模型组（P均〈0.05）。②ALI模型组MDA含量显著高于生理盐水对照组（P〈0.01）,SOD和GSH-Px水平却明显低于生理盐水对照组（P〈0.01）。大剂量胆红素干预组肺匀浆中MDA含量明显低于ALI模型组（P〈0.01）,而肺匀浆中的SOD活性和GSH-Px含量显著高于ALI模型组（P〈0.01,P〈0.05）且与生理盐水对照组差异无统计学意义。小剂量胆红素干预组MDA含量明显高于正常对照组（P〈0.05）,而SOD活性和GSH-Px含量显著低于正常对照组（分别P〈0.05、P〈0.01）且与ALI模型组差异无统计学意义。结论 胆红素通过其抗氧化作用对抗大鼠ALI并且存在剂量依赖性。

Objective To investigate the effects of bilirubin with different doses on LPS-induced acute lung injury （ALl） in rats and its possible mechanism. Methods Forty male Wistar rats （200-250 g） were randomly divided into four groups： the control group, the ALl model group, the low dose and the high dose pre-treatment bilirubin group. Histopathological examination, biological markers for the lung specimens and oxidative/antioxidative parameters in the homogenate of the rat lungs were determined. Results OThe ALl model group, the biological markers of ALl including lung index （LI）, the contents of total protein, cell counts and neutrophil percent age in bronchoalveolar lavage fluid （BALF）, lung permeability index （LPI） significantly increased compared with the control group （P〈0.01）. Pathologic changes decreased. The content of MDA in the homogenate of the lung tissues were significantly high （P〈0.01）, however the level of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） were decreased （P 〈 0.01）. ② Two pretreatments with bilirubin inhibited the LPS-induced changes in lung injury parameters, but there were distinctions between two groups. Conclusion Biliruhin might significantly alleviate the degree of ALl by antioxidation. These effects were concerned with the different doses of bilirubin.