依达拉奉对脂多糖引起的小鼠急性肺损伤的保护效应研究

Therapeutic efficacy of Edaravone for LPS-induced acute lung injury in mice

关键词:  依达拉奉  脂多糖  急性肺损伤

Key words:  Edaravone  lipopolysaccharide  acute lung injury

摘要:

[目的] 探讨依达拉奉在急性肺损伤当中的保护效应及其可能的机制。 [方法] 成年C57小鼠54只被随机等分为3组：正常组(假手术组)，对照组(LPS+生理盐水)和实验组(LPS+依达拉奉)。将对照组和实验组小鼠，采用气道内注入LPS溶液(2 mg/mL)1 mL/kg 造急性肺损伤模型,正常组小鼠不注。实验组小鼠尾静脉注射依达拉奉溶液(2 mg/mL)2.5 mL/kg，对照组小鼠注射等体积生理盐水。24 h后，每组取6只小鼠腹腔注射过量麻醉戊巴比妥(100 mg/kg)，后断头处死，取肺组织用于组织学及丙二醛(MDA)、超氧化物歧化酶(SOD)、TNF-α，IL-1β和IL-6的检测。每组余下的12只小鼠用做生存率实验，每12 h观测1次并记录小鼠存活的情况，观察周期为4 d。 [结果] 实验组小鼠生存率明显高于对照组（P<0.05）；LPS刺激后，小鼠肺组织内的MDA含量由(1.41±0.119) nmol/mg 上升到(4.48±0.159) nmol/mg, 而依达拉奉治疗后则降到(2.56±0.157) nmol/mg (P<0.01)；LPS刺激后，小鼠肺组织内的SOD活力由(12.86±1.49) U/mg 下降到(8.95±1.02) U /mg, 而依达拉奉治疗后则上升至(10.69±1.77) U /mg (P<0.01)；同时，LPS刺激后，小鼠肺组织内的TNF-α，IL-1β和IL-6含量分别由(47.89±4.71) pg/mg、(79.39±3.45) pg/mg和 (81.9±6.39) pg/mg上升到(300.48±12.18) pg/mg、(717.99±35.01) pg/mg和 (428.99±21.89) pg/mg, 而依达拉奉治疗后小鼠肺组织的含量则降到(191.84±6.43) pg/mg、(236.87±13.46) pg/mg和 (136.92±12.47) pg/mg。病理结果显示: 依达拉奉减轻了LPS引起的肺水肿，弥漫性出血和炎性细胞的浸润等症状。 [结论] 依达拉奉可以减轻LPS引起的急性肺损伤。

Abstract:

[Objective] To investigate the protective effects of edaravone treatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI). [Methods] Fifty-four mice were randomized into 3 groups: normal group (Sham operation), control group (LPS + physiological saline) and experiment group (LPS + Edaravone). The mice in control and experiment group were induced ALI by intra-tracheal LPS solution (2 mg/kg body weight). The mice in experiment group were given Edaravone solution (2 mg/mL) 2.5 mL/kg body weight and the mice in control group were given saline at the same volume. At 24 h post-injury, 6 mice in each group were killed and their lung tissues were isolated and assayed for malonaldehyde (MDA), superoxide dismutase activity(SOD), TNF-α, IL-1β, IL-6 and histological examination. The remained 12 mice in each group were used for monitoring the survival rate of mice every 12 h for 4 days. [Results] Our experiments exhibited that the survival rate of experiment group was higher than control group (P<0.05). After LPS stimula tion, MDA content in the lung tissues was increased from (1.41±0.119) nmol/mg to (4.48±0.159) nmol/mg, whereas it was decreased to (2.56±0.157) nmol/mg in the Edaravone treatment group (P<0.01). After LPS stimulation, SOD activity in the lung tissues was decreased from (12.86±1.49) U/mg to (8.95±1.02) U /mg, whereas it was increased to (8.95±1.02) nmol/mg in the Edaravone treatment group (P<0.01). After LPS stimulation, TNF-α，IL-1β and IL-6 content in the lung tissues was increased from (47.89±4.71) pg/mg，(79.39±3.45) pg/mg and (81.9±6.39) pg/mg to (300.48±12.18) pg/mg，(717.99±35.01) pg/mg and (428.99±21.89) pg/mg, whereas they were decreased to (191.84±6.43) pg/mg，(236.87±13.46) pg/mg and (136.92±12.47) pg/mg in the Edaravone treatment group. Edaravone treatment further attenuated lung edema, inflammatory cell infiltrations, widened alveolar septum, and diffuse hemorrhage. [Conclusions] In conclusion, our data demonstrated that ameliorated LPS-induced ALI.