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.
出处
《中华医学杂志》
CAS
CSCD
北大核心
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)