盐酸羟考酮注射液对大鼠急性肺损伤的保护作用及机制分析  

Protective effects of oxycodone on lipopolysaccharide-induced acute lung injury in rats

作　　者：杨波[1] 张卫东[1] 夏彦民 张志培[2] 李磊[1] 张亮[1] 王文辰[2] 王振东[2] 李晓平[1] 

机构地区：[1]天津市第一中心医院胸外科,300192 [2]第四军医大学唐都医院胸外科

出　　处：《中华医学杂志》2016年第31期2498-2501,共4页National Medical Journal of China

基　　金：国家自然科学基金（81070062）

摘　　要：目的探讨盐酸羟考酮注射液对大鼠急性肺损伤的保护作用及其机制。方法雄性sD大鼠随机分成4组：对照组；盐酸羟考酮注射液组（oxycodone组）；脂多糖组；脂多糖＋盐酸羟考酮注射液组（LPS＋oxycodone组）。模型建立成功后，麻醉处死大鼠，运用支气管肺泡灌洗（BALF）收集上清液，酶联免疫吸附实验检测炎症因子如白细胞介素1B（IL-1B）、肿瘤坏死因子仪（TNF—d）和高迁移率族蛋白1（HMGB-1）的水平；湿干重比值（W／D）的测定，观察肺组织水肿情况；苏木精-α红染色法用于观察损伤肺组织病理改变、肺泡腔出血以及中性粒细胞浸润；原位末端转移酶标记技术用于检测细胞凋亡情况；蛋白印迹法检0n．0Toll样受体4（TLR4）蛋白水平表达。结果与脂多糖组相比，羟考酮注射液显著缓解肺泡腔出血和中性粒细胞浸润，降低W／D比值（5．60±0．24比6．80±0．27）；羟考酮注射液抑制炎症因子IL-1B[（1208±15）pg／m1]、TNF-α[（1660±14）pg／m1]、HMGB-1[（61±4）pg／m1]的释放；羟考酮注射液降低细胞凋亡指数（18．6％-4-0．5％）。此外，羟考酮注射液抑制TLR4蛋白的相对表达水平（1．20．4-0．15），差异有统计学意义（P〈0．05）。结论盐酸羟考酮注射液通过抑制TLR4信号通路的激活，对大鼠急性肺损伤具有保护作用。Objeetive To analyze the role of oxycodone in acute lung injury （ALl） induced by lipopolysaccharide （LPS） in rats. Methods Male SD rats were randomly allocated into 4 groups：control group, oxycodone group, LPS group, LPS ＋ oxycodone group. The effects of oxycodone on LPS-induced neutrophils influx, inflammatory cytokines release, pulmonary edema, apoptotic cell were examined. In addition, the toll-like receptor 4 （TLR4） in lung tissues was detected by Western blotting. Results Oxycodone significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratio, was markedly decreased by oxycodone （5.60 ± 0. 24 vs 6. 80 ± 0. 27, P 〈 0. 05 ）. Moreover, oxycodone decreased the productions of the inflammatory cytokines including IL-1β ,TNF-α, HMGB-I （ （ 1 208 ± 18） pg/ml, （ 1 660 ± 14） pg/ml, （61± 4） pg/ml , all P 〈0. 05）. Oxycodone treatment also reduced the concentration of apoptosis in lung tissues（ 18.6%± 0. 5% ,P 〈 0. 05 ）. Furthermore, the expression of TLR4 was significantly suppressed by oxycodone treatment in lung tissues （ 1.20 ± 0. 15, P 〈 0. 05）. Conclusions Oxycodone exerts protective effects on LPS-induced ALl in rats. The potential mechanism of this action may attribute partly to the inhibition of TLR4 activation.

关 键 词：急性肺损伤 TOLL样受体4 羟考酮 

分 类 号：R563[医药卫生—呼吸系统]