山莨菪碱对急性肺损伤时肺泡巨噬细胞分泌细胞因子的干预探讨

Studies of Anisodamine in treatment of ALI and its effects on cytokine secretion in alveolar macrophages

目的 观察山莨菪碱 (6 5 4- 2 )对急性肺损伤 (ALI)大鼠肺泡巨噬细胞 (AM)分泌肿瘤坏死因子 -α(TNF -α)、白细胞介素 - 6 (IL - 6 )的影响 ,探讨其对ALI治疗作用的可能机制。方法 复制ALI大鼠模型。实验动物随机分为ALI模型组、6 5 4- 2治疗组、对照组 ,进行各组大鼠动脉血气、肺湿 /干 (W/D)值测定及肺组织病理学光镜检查。分离培养各组大鼠肺泡巨噬细胞 ,采用生物活性法进行AM上清液TNF -α、IL - 6测定。结果 6 5 4- 2治疗组大鼠AM分泌TNF -α[(38.98± 4.5 1)KU/L]和IL - 6 [(2 0 .82± 6 3)kU/L]的水平明显低于ALI组 [TNF -α为 (6 8 2 7± 9 13)kU/L ,P <0 0 0 1;IL - 6为 (33 84± 9 0 2 )kU/L ,P <0 0 1],并能使血气改善 (P <0 0 5 )、W/D值下降 (P <0 0 5 ) ,肺组织损伤程度减轻。结论 6 5 4- 2对ALI大鼠肺泡巨噬细胞过度活化、分泌TNF -α、IL - 6具有显著抑制作用 。

Objective To explore the mechanism of anisodamine(654-2) in the treatment of acute lung injury(ALI),the effect of 654-2 on TNF-α and IL-6 levels released by alveolar macrophages were investigated in rats.Methods ALI rats model was made by injection of lipopolysaccharide(LPS) intravenously.48 rats were equally divided into three groups:ALI model group,654-2 treatment group and normal control group.The bloods air,lung wet/dry (W/D) weight and pathological examination were made in each groups.Then the alveolar macrophages of each group were separated and cultured,the quantities of TNF-α and IL-6 were measured by bioassa methods.Results TNF-α [(38.98±4.51)kU/L] and IL-6[(20 82±6 3)kU/L]levels released by alveolar macrophages in 654-2 treatment group were significantly lower than those of ALI group [TNF-α(68 27±9 13)kU/L, P <0 001];IL-6[(33 84±9 02)kU/L, P <0 01]and 654-2 can also improve the blood airs levels( P <0 05),reduce the W/D value ( P <0 05) and relieve the lung injury observed by histological examination.Conclusion 654-2 can inhibit the excessive activation and TNF-α,IL-6 secretion of alveolar macrophages,prevent the occurrance progression of ALI in rats. [