氨溴索联合地塞米松对大鼠急性呼吸窘迫综合征早期的肺保护作 用简

目的 给予脂多糖（LPS）诱导的急性呼吸窘迫综合征大鼠氨溴索（AMB）及地塞米松（DXM）干预后,观察细胞因子的表达及病理学变化,探讨两药联合对急性呼吸窘迫综合征早期的肺保护作用及其可能的机制.方法 SD大鼠42只,随机分成6组,每组7只：空白对照组（C组）,阴性对照组（N组）,阳性对照组（L组）,AMB干预组（A组）,DXM干预组（D组）和AMB联合DXM干预组（AD组）.C组无处理,N组自尾静脉注入生理盐水2 mL,余各组均注入脂多糖（LPS）5 mg/kg,各干预组分别给予AMB（100 mg/kg）、DXM（6 mg/kg）.各组于6h后进行血气分析;测定肺组织湿重与干重比（W/D）;制备肺匀浆,测定其中髓过氧化物酶（MPO）、肿瘤坏死因子-α（TNF-α）、白介素-1β （IL-1β）水平并观察肺组织病理变化.结果 与对照组比较,各干预组血气分析指标明显改善氧分压（PO2）：C组：（106.47.8）mm Hg（1 mm Hg=0.133 kPa）,N组：（104.1±7.2）mm Hg,L组：（69.0±4.5）mm Hg,A组：（77.3±5.4）mm Hg,D组：（78.8±6.2）mm Hg,AD组：（86.8±5.6）mm Hg],而在W/D比C组：（4.42±0.12）,N组：（4.39±0.13）,L组：（5.42±0.05）,A组：（4.95±0.16）,D组：（4.90±0.12）,AD组：（4.73±0.10）、MPOC组：（0.35±0.06）U/mg,N组：（0.33±0.04）U/mg,L组：（0.85±0.05）U/mg,A组：（0.55±0.04）U/mg,D组：（0.58±0.05）U/mg,AD组：（0.48±0.04）U/mg]及TNF-αC组：（228.2±18.3）ng/L,N组：（234.6±19.3）ng/L,L组：（719.4±60.2）ng/L,A组：（479.1±29.2）ng/L,D组：（310.9 ±20.5）ng/L,AD组：（294.7±17.5）ng/L]、IL-1βC组：（0.112±0.005）μg/L,N组：（0.116±0.002）μg/L,L组：（0.189±0.008）μg/L,A组：（0.144±0.009）μg/L,D组：（0.139±0.013）μg/L,AD组：（0.130±0.007） μg/L]各项指标检测均明显降低;光镜下观察C组及N组肺组织学正常,L组出现弥漫性肺泡间隔增厚、渗出及水肿明显、透明膜形成,同时可见大量炎症细胞浸润,肺间质弥漫性出血,而A、D及AD组光镜下上述病理表现明显减轻.上述结果在两药联合干预组改善更为明显.结论 氨溴索与地塞米松合用对脂多糖诱导的急性呼吸窘迫综合征大鼠具有协同肺保护作用,其机制考虑为两者的共同抗炎及促肺泡表面物质生成作用所致.

Effects of Ambroxol combined with Dexamethasone on acute lung injury induced by lipopolysaccharide in rats

Objective To observe the effects and possible mechanismsof Ambroxol （AMB）/Dexamethasone （DXM）-coadministration on the changes of inflammatory cytokines expression as well as the pathological variations of lung in lipopolysaccharide （LPS）-induced acute respiratory distress syndrome （ARDS）.Methods 42 SD rats were divided randomly into 6 groups with 7 each：blank control group （group C）,negative control group （group N）,positive control group （group L）,AMB intervention group （group A）,DXM intervention group （group D）,AMB and DXM combined intervention group （group AD）.Group C was without treatment,group N was given 2 mL of 0.9% NS injection via tail vein; all the other four groups were given LPS of 5 mg/kg; the intervention groups were given AMB （100 mg/kg）,DXM （6 mg/kg）.All the rats were killed in 6 hours to analysis arterial blood gas and lung tissue wet/dry weight ratio,and then to observe the levels of myeloperxidase （MPO）,tumor necrosis factor-α （TNF-α）,interleukin-1 （IL-1β）,as well as the pathological changes in lung.Results Compared with group C,the blood gas analysisimproved significantly PO2：group C：（106.4±7.8） mm Hg （1 mm Hg=0.133 kPa）,group N：（104.1±7.2） mm Hg,group L：（69.0±4.5） mm Hg,group A：（77.3±5.4） mm Hg,group D：（78.8±6.2） mm Hg,group AD：（86.8±5.6） mm Hg],while the level of W/D ratio group C：（4.42±0.12）,group N：（4.39±0.13）,group L：（5.42±0.05）,group A：（4.95±0.16）,group D：（4.90±0.12）,group AD：（4.73±0.10）],MPO group C：（0.35±0.06） U/mg,group N：（0.33±0.04） U/mg,group L：（0.85±0.05） U/mg,group A：（0.55±0.04） U/mg,group D：（0.58±0.05） U/mg,group AD：（0.48±0.04） U/mg],TNF-α group C：（228.2±18.3） ng/L,group N：（234.6±19.3） ng/L,group L：（719.4±60.2） ng/L,group A：（479.1±29.2） ng/L,group D：（310.9±20.5） ng/L,group AD：（294.7±17.5） ng/L],and IL-1β group C：（0.112±0.005） μg/L,group N：（0.116±0.002） μg/L,group L：（0.189±0.008） μg/L,group A：（0.144±0.009） μg/L,group D：（0.139±0.013） μg/L,group AD：（0.130±0.007） μg/L] decreased significantly in all the intervention groups.The group C and group N showed normal under optical microscope.Diffused alveolar septum thickening,exudation,edema,ARDS membrane,and the inflammatory granulocyte infiltrating and significant spotty hemorrhage were observed in group L.The histological changes of group A,D,and AD were better than group L.All the results were much more significantly changed in the group which two drugs were combined.Conclusion The combination use of AMB and DXM has cooperative protective effects on acute respiratory distress syndrome induced by LPS in rats.The mechanism may be associated with the common anti-inflammatory effects,the promotion effect of pulmonary surfactant,and also probably related to the common anti-fibrosis and antioxidant effect,leading to the reconstruction of the balance of oxidation and antioxidant system as well as the resluting lung protection.