黄芩苷对急性肺损伤大鼠肺泡液体清除作用的研究

Effect of baicalin on alveolar fluid clearance in rats with acute lung injury

摘要:

目的：用脂多糖（lipopolysaccharides，LPS）诱导大鼠急性肺损伤，探讨黄芩苷对大鼠肺泡液体清除的效应。方法：将SD大鼠分为空白对照组、LPS诱导急性肺损伤（acute lung injury，ALI）组及ALI+黄芩苷预处理组。根据黄芩苷预处理浓度再分为10、50、100 mg/kg 3个亚组。经LPS及不同浓度黄芩苷作用不同时间（2、4、6 h）后，计算肺湿/干重（W/D）比值，放射免疫分析法测定大鼠肺组织中环磷酸腺苷（cyclic adenosine monophosphate，cAMP）水平，观察肺组织病理学改变，并测量肺泡液体清除率（alveolar fluid clearance，AFC）变化。每组或亚组各5只大鼠。结果：黄芩苷预处理后，ALI大鼠肺组织含水量[黄芩苷10 mg/kg组（7.94±1.14）；黄芩苷50 mg/kg组（6.13±1.34）；黄芩苷100 mg/kg组（5.38±1.43）]较模型组（9.88±1.53）明显减少（P＜0.05），cAMP含量[黄芩苷10 mg/kg组（381.00±60.51） pmol/g；黄芩苷50 mg/kg组（493.40±63.93） pmol/g；黄芩苷100 mg/kg组（582.40±47.44） pmol/g]较模型组[（265.8±62.39） pmol/g]明显增加（P＜0.05），两者结果均随着预处理黄芩苷的浓度增加而增加。ALI+黄芩苷组较ALI组肺间质水肿明显减轻，炎症细胞浸润明显减少。黄芩苷预处理组各时间点AFC明显高于ALI组，并随黄芩苷预处理浓度增加而增加（P＜0.05），且大鼠肺组织内cAMP水平与AFC呈正相关（r=0.984，P=0.002）。但在加入阿米洛利后，各组AFC明显下降，且各组间无明显差异（P＞0.05）。结论：黄芩苷能够改善ALI大鼠肺泡液体清除，其可能途径为增加细胞内cAMP水平从而调节上皮钠通道功能。

Abstract:

Objective：To research the effect of baicalin on alveolar fluid clearance（AFC） in rats with acute lung injury（ALI） induced by lipopolysaccharides（LPS）. Methods：Sprague-Dawley（SD） rats were randomly divided into control group，ALI group and baicalin pretreatment group（ALI+baicalin group），with 5 rats in each group. The ALI+baicalin group was further divided into three subgroups with different concentrations（10，50，100 mg/kg）. SD rats in each group were killed for measurement of ratio of wet to dry（W/D） weight of lung tissue，cyclic adenosine monophosphate（cAMP） level by radioimmunoassay，pathological changes and AFC at 2，4 and 6 h. Results：Compared with ALI group[W/D weight：（9.88±1.53）；concentration of cAMP：（265.80±62.39） pmol/g]，baicalin pre-treatment[baicalin 10 mg/kg group：（7.94±1.14）；baicalin 50 mg/kg group：（6.13±1.34）；baicalin 100 mg/kg group：（5.38±1.43）] significantly decreased W/D weight of lung tissue（P＜0.05），and [baicalin 10 mg/kg group：（381.00±60.51） pmol/g；baicalin 50 mg/kg group：（493.40±63.93） pmol/g；baicalin 100 mg/kg group：（582.40±47.44） pmol/g] significantly increased concentration of cAMP in lung tissue（P＜0.05） in a dose-dependent manner with increasing doses. Interstitial edema and inflammatory cell infiltration were markedly decreased when being pretreated with baicalin. AFC was significantly increased in ALI+baicalin group in a dose-dependent manner at different intervals（P＜0.05）. Meanwhile，cAMP concentration in lung tissue was positive correlated with AFC（r=0.984，P=0.002）. Addition of amiloride to the instillate decreased fluid clearance significantly. Baicalin or LPS had no significant effect on AFC in rats with ALI as amiloride being added in the instillate（P＞0.05）. Conclusion：Baicalin alleviates low AFC in rats with ALI probably by increasing intercellular cAMP level to modulate epithelial sodium channel.