穿心莲内酯对内毒素诱导急性肺损伤大鼠TLR4、CD14、MD2 mRNA表达的影响

Influence of Andrographolide on Expression of TLR4、CD14、MD2 mRNA in Acute Lung Injury in Rats Induced by Lipopolysaccharide

目的:探讨穿心莲内酯(andrographolide,AND)对脂多糖(LPS)诱导急性肺损伤大鼠TLR4(Toll-like receptor 4)、CD14、髓样分化蛋白-2(MD2)mRNA表达的影响。方法:SD大鼠36只,随机分6组:对照组、LPS组;穿心莲内酯组,每组再分为4 h、8 h两个亚组。向气管内滴注脂多糖(LPS)(10 mg/kg)建立大鼠急性肺损伤模型,穿心莲内酯组LPS滴注后立即予穿心莲内酯注射液尾静脉注射干预,分别于LPS处理后4 h、8 h取血和肺组织,测定各组大鼠动脉血氧分压(Pa O2),测肺湿干比重(wet weight/dry weight,W/D);测定肺组织TLR4、CD14、MD2 mRNA表达的变化;观察各组大鼠肺组织的病理改变。结果:LPS组大鼠Pa O2呈进行性降低;肺体质量指数明显增加;肺组织TLR4、CD14、MD2 mRNA表达明显增加;肺组织病理示肺内中性粒细胞大量浸润,伴出血、透明膜形成;穿心莲内酯组的各项指标均较LPS损伤组减轻。结论:穿心莲内酯能降低LPS诱导急性肺损伤大鼠TLR4、CD14、MD2 mRNA的表达,减轻肺组织的病理损害。

Objective：To investigate the changes of TLR4, CD14 and MD2 mRNA expression in acute lung injury in rats induced by lipopolysaccharide. Methods ： Thirty - six SD rats were randomly divided into six groups ： control group ; LPS group;andrographolide group, each grope had two subgrope,4 hours and 8 hours after LPS injection. Rat model of ALI was reproduced by intratracheal instillation of lipopolysaccharide （LPS） in a dose of 10 mg/kg . At the same time, the rats suffered from acute lung injury were treated with andrographolide injection. The blood and lung tissue samples were collected at 4 and 8h after LPS injection , Arterial gas analysis and lung wet/dry weight ratio were analyzed . The expression of TLR4, CD14 and MD2 mRNA were measured by real time fluorescenl polymerase chain reaction（PCR） , and the pathological changes of lung were observed. Results ： In LPS group the partial pressure of oxygen in artery （ PaO2 ） was progressively decreased, while lung wet/dry weight ratio and expression of TLR4, CD14 and MD2 mRNA were in- creased, and lung pathology showed severe polymorphonuclear leukocytes infiltration with bleeding and hyaline mem- branes formation. In andrographolide group the values of all above parameters were alleviated. Conclusion ： Andrographol- ide can decrees expression of TLR4,CD14 and MD2 mRNA in acute lung injury in rats induced by lipopolysaccharide, and attenuate pathological lung tissue injury.