氨溴索联合地塞米松对脂多糖诱导的急性肺损伤大鼠肺表面活性蛋白A的影响

Effects of ambroxol combined with dexamethasone on pulmonary surfactant protein A in acute lung injury rats induced by lipopolysaccharide

目的观察氨溴索和地塞米松联用对脂多糖诱导的急性肺损伤(ALI)大鼠肺表面活性蛋白A(SP-A)表达的影响。方法 SD大鼠42只,随机分成六组,每组7只。空白对照组无处理,阴性对照组自尾静脉注入生理盐水2 mL。其余四组均给予脂多糖5 mg·kg-1,在此基础上氨溴索组予氨溴索100 mg·kg-1,地塞米松组予地塞米松6 mg·kg-1,联合用药组予氨溴索60 mg·kg-1+地塞米松4 mg·kg-1。检测各组血气分析指标、肺组织湿干重比及病理学改变,采用免疫组化和RT-PCR测定各组肺组织SP-A含量及mRNA表达。结果空白对照组和阴性对照组各项指标均无显著差异(P>0.05)。与对照组比较,模型组大鼠动脉血pH值和PaO2降低,肺组织湿干重比增高,SP-A含量及其mRNA表达均下降,差异均有显著意义(P<0.05),病理损伤明显。与模型组比较,各给药组pH值和PaO2增高,肺组织湿干重比降低,SP-A含量及其mRNA表达均升高(P<0.05),病理损伤明显改善,联合用药组改善优于氨溴索组和地塞米松组(P<0.05)。结论氨溴索与地塞米松可能通过提高肺组织SP-A含量对ALI大鼠起保护作用,两药合用效果更佳。

AIM To observe the effects of ambroxol （Amb） /dexamethasone （DXM） co-administration on the changes of pulmonary surfactant protein A （SP-A） in lipopolysaccharide （LPS） -induced acute lung injury （ALI） rats. METHODS Forty-two SD rats were divided randomly into 6 groups with 7 each： blank control group （group C）, negative control group （group N）, model group （group M）, Amb intervention group （group A）, DXM intervention group （group D）, Amb and DXM combined intervention group （group AD）. The group N was given normal saline 2 mL via tail vein, while no treatment in the group C. All the other four groups were given LPS 5 mg·kg^-1 and group A was given Amb 100 mg·kg^-1, group D was given DXM mg·kg^-1, group AD was given Amb 60 mg·kg^-1 ＋ DXM 4 mg·kg^-1. The indexes of blood gas analysis, wet to dry （W/D） of lung and lung tissue pathology were examined. The expression of SP-A and the level of SP-A mRNA was measured with immunohistochemistry and reverse transcription-polymerasechain reaction （RT-PCR）. RESULTS There was no significant difference in each index between group C and group N （P 〉 0.05）. Compared with those in the group C, the levels of arterial blood pH and PaO2 decreased, W/D of lung increased, and the expression of SP-A content and mRNA decreased in the group M （P 〈 0.05）, and with obvious pathological injury. Compared with those in the group M, pH and Pa02 increased, W/D of lung decreased, the expression of SP-A content and mRNA increased in each drug group （P 〈 0.05）, and the pathological damage was improved. The improvement was better in the group AD than group A and group D （P 〈 0.05）. CONCLUSION Both Amb and DXM can improve the level of SP- A in ALI rats induced by LPS, and combination of them are better.