高压氧联合甲基强的松龙促进兔极快速减压后肺损伤恢复

Effect of methylprednisolone combined with hyperbaric oxygen on acute lung injury induced by rush decompression in rabbits

目的探讨高压氧联合甲基强的松龙对极快速减压致兔肺损伤的治疗作用。方法26只成年雄性新西兰兔，按数字表法随机分为对照组6只、模型组10只，治疗组10只。模型组和治疗组采用真空泵抽气方法建立极快速减压致肺损伤兔模型。出舱后即刻，各组处死3只测定肺湿干质量比。模型组和对照组其余动物常规喂养3d，不治疗；治疗组静脉注射甲基强的松龙（1mg／kg）后行高压氧治疗（表压0．10MPa，稳压吸氧2h），每天1次，连续治疗3d。3d后处死所有动物，观察各组兔肺湿干质量比、病理形态学、肺组织TNF．Ot、IL．1fl含量及NF．s：Bp65mRNA表达的变化。结果在极快速减压后即刻和3d后，模型组肺湿干质量比（分别为5．29±0．26，3．20±0．21）较对照组（分别为2．32±0．54，2．15±0．40）增高（P〈0．01），肺组织渗出和炎性浸润明显。经高压氧和甲基强的松龙联合治疗3dg，治疗组肺湿干质量比（2．34±0．49）明显降低，与对照组（2．15±0．40）比较差异无统计学意义（P〉0．05），与模型组（3．20±0．21）比较差异有统计学意义（P〈0．05）。3d后，模型组肺组织匀浆液TNF-α、IL-1β含量[分别为（9．53±1．28）、（20．34±1．87）ng／L）]较对照组[分别为（6．42-4-0．95）、（15．63±1．85）ng／L）]明显增高（P〈0．05或P〈0．01）；NF—KBp65mRNA相对表达量（1．32±0．48）也较对照组（0．35±0．07）增高（P〈0．05）。经过3d高压氧和甲基强的松龙联合治疗后，治疗组急性病理损伤评分（4．43±0．93）与模型组（8．56±1．73）比较明显改善（P〈0．01），与对照组（0．97±0．17）比较仍然较高（P〈0．01）；肺组织匀浆液TNF．O／、IL—lfl含量[分别为（7．17±0．65）、（16．63±0．57）ng／L]较模型组[分别为（9．53±l。28）、（20．34±1．84）ng/L）]明显降低（P〈0．05）；NF—κBp65mRNA相对表达量（0．43±0．15）也较模型组（1．32．±0．48）显著降低（P〈0．05）。结论高压氧联合甲基强的松龙对极快速减压肺损伤有积极的治疗作用，其中NF—κB炎性途径受抑可能是作用机制之一。

Objective To explore the effect of methylprednisolone combined with HBO on acute lung injury （ALl） induced by rush decompression. Methods Twenty-six male healthy rabbits were randomly divided into the normal control group （ n = 6 ） , the model group and the .combined therapy group. Four animals in the model group and the combined therapy group died, following development of the ALI model by rush decompression by using vacuum pumps. Then, the remaining 24 animals were randomly divided into the model group and the combined therapy group, each consisting of 12 animals. The moment after the animals were surfaced from the chamber, 4 animals in each group were sacrificed for the detection of wet/dry ratio of the lung tissue. The remaining animals in the model and control groups were given normal feeding for 3 days, without any treatment. Following injection of methylprednisolone （ l mg/kg）, the animals in the combined therapy group were exposed to HBO （0.1 MPa gauge pressure, breathing oxygen for 2 hours） , one session a day for a succession of 3 days. Three days later, observations were made on the wet/dry ratio of the lung tissue, pathologic morphology, concentrations of TNF-α and IL-1β, and the expressions of NF-κB p65 mRNA. Results The moment and 3 days after rush decompression, the wet/dry values of the animals in the model group were （5.29±0.26,3.20 ±0.21 ） , which were higher than those of the animals in the control group （2.32 ＋0.54, 2.15 ± 0.40） （P 〈 O. O1 ）. Significant pulmonary exudation and inflammatory infiltration could obviously been seen. Three days after treatment with methylprednisolone combined with HBO therapy, the wet/dry value of the animals in the treatment group decreased significantly （ 2.34 4- 0.49 ） , without statistical significance, when compared with that of the control group. However, statistical significance could be noted, when compared with that of the model group. Three clays later, concentrations of TNF-α and IL-1/3 of the model group increased 9.53 ± 1.28 ）, （ 20.34± 1.87 ） ng/L） ], which were significantly higher than those of the control group 6.42＋0.95）,（15.63±1.85）ng/L）l （P〈0.05 or P〈0.01）. The expressions of NF-κB p65 mRNA ± 32 ± 0.48 ） also increased, when compared with those of the control group （0.35 ＋ 0.07 ） （ P 〈 0.05 ）. After 3 days of combined treatment with methylprednisolone and HBO, acute lung injury score of the treatment group was（4.43 ± 0.93 ）, which showed a significant improvement, when compared with that of the model group （8.56 ± 1.73 ） （P 〈 0.01 ）. Nevertheless, it was still rather high, when compared with that of the control group（0.97 ±0. 17）（P 〈 0.01 ）. The concentrations of TNF-α and IL-1β in the homogenates decreased [ （7.17±0.65） , （ 16. 63 ± 0. 57 ） ng/L] , which were significantly lower than those of the model group I （9.53 ± 1.28） , （20.34± 1.84） ng/L） （ P 〈 0.05 ）. In the meantime, the expression of NF-KB p65 mRNA also declined markedly （0.43 ± 0.15 ） , when compared with that of the model group （ 1.32 ± 0.48 ） （ P 〈 0.05）. Conclusions The combined treatment of methylprednisolone and HBO could produce positive effects on acute lung injury induced by rush decompression, the inhibition in the expression of NF-κB p65 might be one of the mechanisms involved.