雾化吸入全氟化碳联合肺表面活性物质对急性肺损伤兔的作用

摘要

目的 观察全氟化碳(PFC)联合肺表面活性物质(PS)雾化吸入对急性肺损伤(ALI)兔的影响.方法 将32只新西兰家兔按随机数字表法分为ALI组、联合用药组、PFC组、PS组,每组8只.采用生理盐水整肺灌洗法制备ALI模型.联合用药组于制模后雾化吸入全氟溴辛烷/二棕榈酰磷脂酰胆碱(PFOB/DPPC)乳剂3 mL/mg,PFC组、PS组于制模后分别雾化吸入PFOB、DPPC各3 mL/mg,ALI组雾化吸入等量生理盐水.观察各组动物制模前30 min(基础值)、制模后1 h及给药后0 min、30 min、2 h、4 h呼吸频率(RR)、氧合指数(OI)、动态肺顺应性(Cdyn);计算肺系数和肺通透指数(LPI);采用双抗体夹心酶联免疫吸附试验(ELISA)测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平;取肺组织,经肉眼及显微镜观察肺组织病理学改变.结果 ALI组制模后OI、Cdyn迅速下降,RR明显增快,且肺组织出现明显水肿、出血及炎症渗出.联合用药组及PFC组OI于用药后0 min即较ALI组明显升高〔mmHg(1 mmHg=0.133 kPa):231.0±16.7、221.4±19.0比189.5±21.0,均P<0.05〕,而PS组于用药后4 h才显著高于ALI组(mmHg:297.0±20.7比243.3±36.7,P<0.05);联合用药组RR于用药后30 min即较ALI组明显减慢(次/min:151.1±13.3比178.5±32.0,P<0.05),而PFC组、PS组均于用药后4 h才显著高于ALI组(次/min:129.3±14.3、133.1±13.9比157.5±32.5,均P<0.05);3个用药组Cdyn均于用药后0 min即较ALI组明显升高(mL/cmH2O:1.64±0.10、1.45±0.10、1.43±0.09比0.57±0.05,均P<0.05);LPI、肺系数及炎症因子水平均较ALI组明显降低〔LPI(×10-5):4.21±0.42、4.76±0.55、4.87±0.49比5.56±0.52,肺系数:8.04±0.58、8.90±0.88、9.22±0.71比10.85±0.73,TNF-α(ng/L):50.05±4.91、56.18±5.54、63.60±5.96比73.60±5.27,IL-1β(ng/L):34.27±4.55、40.29±5.03、48.13±6.38比54.71±4.26,均P<0.05〕,且肺水肿、充血及炎症细胞浸润均明显改善〔病理学评分(分):3.74±0.58、4.50±0.75、5.29±0.72比6.13±0.72,均P<0.05〕;联合用药组用药后0 min、30 min、4 h Cdyn均显著高于PFC组、PS组(均P<0.05),而PFC组与PS组间未见明显差异;联合用药组肺系数、LPI、炎症因子水平及病理学评分指标均明显低于PFC组及PS组,PFC组炎症因子水平及病理学评分较PS组改善更加显著(均P<0.05).结论 在整肺灌洗ALI模型中,PFOB联合DPPC雾化吸入可能通过输送氧气、降低促炎因子水平、补充肺PS并影响其在肺表面的分布,从而改善氧合及肺顺应性,减轻肺组织水肿及炎症反应.%Objective To observe the effects of vaporized perfluorocarbon (PFC) combined with exogenous pulmonary surfactant (PS) inhalation on rabbit models of acute lung injury (ALI).Methods Thirty-two New Zealand rabbits were randomly divided into four groups: ALI group, combination treatment group, PFC group, and PS group (each groupn = 8 rabbits). The rabbit model of ALI was induced by the whole lung normal saline lavage. After modeling, in the combined group, 3 mL/kg vaporized perfluorooctyl bromide/dipalmitoylphosphatidylcholine (PFOB/DPPC) emulsion was inhaled, the rabbits in PFC and PS groups were treated with vaporized PFOB emulsion and vaporized DPPC emulsion 3 mL/kg inhalation respectively, and in the ALI group was given the same amount of vaporized normal saline inhalation. In each group, before modeling for 30 minutes (basic value), after modeling for 1 hour and after treatment at 0 minute, 30 minutes, 2 hours, 4 hours, the respiratory rate (RR), oxygenation index (OI), dynamic lung compliance (Cdyn) were observed, and the lung coefficient (LI) and lung permeability index (LPI) were calculated; the levels of serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA); the lung tissue was collected and the lung pathological changes were observed under macroscopic and microscopic observation.Results Aftermodeling, the levels of OI, Cdyn were quickly lowered, RR became significantly elevated, and there were obvious edema, hemorrhage and exudation in lung tissue of ALI group. The levels of OI were significantly increased in combined group and PFC group compared with the level in ALI group after treatment at 0 minute initially [mmHg (1 mmHg = 0.133 kPa): 231.0±16.7, 221.4±19.0 vs. 189.5±21.0, both P < 0.05], while the level of OI in PS group was increased significantly until 4 hours after treatment, being higher than that in ALI group (mmHg: 297.0±20.7 vs. 243.3±36.7,P < 0.05); RR was decreased significantly in combined treatment group at 30 minutes after treatment compared with that in ALI group (bpm: 151.1±13.3 vs. 178.5±32.0,P < 0.05), while the RR in PFC group and PS group were not increased significantly until 4 hours after treatment being higher than that in ALI group (bpm: 129.3±14.3, 133.1±13.9 vs. 157.5±32.5, bothP < 0.05). Compared to ALI group, the three treatment groups resulted in significant improvement in Cdyn right at 0 minute (mL/cmH2O: 1.64±0.10, 1.45±0.10, 1.43±0.09 vs. 0.57±0.05, allP < 0.05), their LPI, LI and inflammatory cytokines were significantly decreased [LPI (×10-5): 4.21±0.42, 4.76±0.55, 4.87±0.49 vs. 5.56±0.52, LI: 8.04±0.58, 8.90±0.88, 9.22±0.71 vs. 10.85±0.73, TNF-α (ng/L): 50.05±4.91, 56.18±5.54, 63.60±5.96 vs. 73.60±5.27, IL-1β (ng/L): 34.27±4.55, 40.29±5.03, 48.13±6.38 vs. 54.71±4.26, allP<0.05], and pulmonary edema, congestion and inflammatory cell infiltration were obviously ameliorated (pathological scores: 3.74±0.58, 4.50±0.75, 5.29±0.72 vs. 6.13±0.72, P < 0.05). Cdyn levels were increased significantly in combined treatment group at 0 minute, 30 minutes, 4 hours after treatment compared with thosein PFC and PS group, but there were no significant differences between PFC and PS group. Levels of LI, LPI, inflammatory factors and pathological scores were decreased significantly in combined treatment group compared with those in PFC and PS group, the degrees of improvement of inflammatory factors and pathological scores in PFC group were more obvious than those in PS group (allP < 0.05).Conclusions PFOB combined with DPPC inhalation can provide greater oxygen delivery, reduce the pro-inflammatory cytokines, supplement PS and influence its distribution on the surface of lung, which might lead to a marked and sustained improvement in oxygenation, pulmonary function and amelioration of lung edema and inflammatory reaction in saline lavage induced lung injury of rabbits.