预防性应用依达拉奉对烟雾吸入性损伤大鼠的肺保护作用

Preventive effect of Edaravone on lung in smoke inhalation injury in rats

目的探讨依达拉奉(edaravone)在烟雾吸入性损伤中对肺的保护作用。方法将32只雄性Sprague-Dawle大鼠采用随机数字表法随机分为4组,每组8只。分别为正常对照组(A组),致伤空白组(B组),致伤依达拉奉预防组(C组),致伤依达拉奉治疗组(D组)。除A组外,其余各组大鼠制作重度烟雾吸入性损伤模型。C组致伤前10min给予腹腔注射依达拉奉9mg/kg,D组致伤后30min给予腹腔注射依达拉奉9mg/kg,B组致伤后30min给予等量0.9%氯化钠溶液,A组无处理。伤后6h留取各组大鼠股动脉血液样本5mL,离心取血清检测肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)含量;留取肺组织制备肺组织匀浆后测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)、肺髓过氧化物酶(MPO)活性。取部分右肺组织经4%甲醛溶液固定后做病理苏木精-伊红(HE)染色切片光镜观察。结果与B组相比,D组TNF-α[(311.8±7.90)pg/mL vs (399.3±8.03)pg/mL]、IL-6[(229.3±7.01)pg/mL vs (367.2±22.67)pg/mL]、MDA[(4.27±0.06)nmol/mg vs (6.30±0.09)nmol/mg]、MPO[(46.22±0.44)U/g vs (72.68±1.14)U/g]显著降低,差异有高度统计学意义(P﹤0.01),SOD[(148.53±2.18)U/mg vs (100.05±1.03)U/mg]及IL-10[(264.7±5.37)pg/mL vs (232.3±7.62)pg/mL]增高,差异有统计学意义(P﹤0.05);C组较B组上述变化更明显,差异有高度统计学意义(P﹤0.01)。光镜下C组和D组较B组肺组织炎细胞浸润减少,肺水肿减轻。结论依达拉奉可能通过抑制自由基的产生及减少部分炎性介质的生成对烟雾吸入性肺损伤起到保护作用,且提前用药效果较好。

Objective To investigate the protective effects of Edaravone on lung in smoke inhalation injury in rats. Methods Thirty-two male Sprague-Dawle （SD） rats were randomly divided into four groups （ n =8） ： normal control group （group A） ,injured group （group B） ,Edaravone prevented group （group C） and Edaravone treated group （group D） . Ten minutes before smoke inhaled injured,the rats in group C were all injected intraperitoneally with Edaravone （9mg/kg） ,while 30 minutes after smoke inhaled injured,the rats in group D were all injected intraperitoneally with Edaravone （ 9 mg / kg） ,and at the same time the group B were injected the same volume normal saline. The rats were treated by no means in the control group. Every group collected the blood samples 5 mL from femoral artery and the lung tissue after smoke inhaled injured at the time of 6 hours. The samples were centrifugalized and tested the levels of tumor necrosis factor-α （ TNF-α） ,interleukin-6 （ IL-6） ,interleukin-10 （ IL-10） in serum as well as the levels of malondialdehyde （ MDA） ,myeloperoxidase （ MPO） ,superoxide dismutase （ SOD） in lung tissues. The histopathological examination was performed with the tissue specimens taken from the apex of right lung. Results Compared with group B,remarked decreases were found in the TNF-α （ 311. 8 ± 7. 90） pg /mL vs （ 399. 3 ± 8. 03） pg/mL,IL-6 （ 229. 3 ± 7. 01） pg/mL vs （ 367. 2 ± 22. 67） pg/mL,MDA （ 4. 27 ± 0. 06） nmol / mg vs （ 6. 30 ± 0. 09） nmol / mg,MPO （ 46. 22 ± 0. 44） U / g vs （ 72. 68 ± 1. 14） U / glevels in group D （ P ﹤0. 01） ,while the levels of SOD （ 148. 53 ± 2. 18） U / mg vs （ 100. 05 ± 1. 03） U / mg and IL-10 （ 264. 7 ± 5. 37） pg / mL vs （ 232. 3 ± 7. 62） pg / mLwere increased （ P 0. 05） ,and the expressions of the above factors were more evident in group C （ P 0. 01） . Histopathological examination showed that inflammatory granulocytes and edema were improved in group C and group D compared with group B. Conclusions Edaravone has protective effects on smoke inhalation injured by anti-oxygen free radical and inhibiting inflammatory mediators production. The effect of Edaravone on smoke inhalation injury is better in prevention.