高压氧治疗肝肺综合征大鼠的实验研究

Experimental study of hyperbaric oxygen therapy in rats with hepatopulmonary syndrome

目的研究高压氧治疗对大鼠肝肺综合征(HPS)的作用。方法采用胆总管结扎术(CBDL)制备HPS动物模型。44只雄性SD大鼠随机分为4组:假手术对照组(Sham组)8只、单纯造模组(CBDL5w组)12只、治疗1周组(HBOT1w组)12只、治疗2周组(HBOT2w组)12只。两治疗组在造模成功后送入高压氧舱治疗,分别治疗1周和2周。Sham组和CBDL5w组大鼠在术后5周,HBOT1w组和HBOT2w组在治疗结束后,进行血气分析、肝功能以及血清一氧化氮(NO)、内皮素-1(ET-1)浓度检测,肝、肺病理检查,并使用激光多普勒血流仪检测肝、肺微循环。结果CBDL5w组大鼠肝功能检测中ALB降低,ALT、AST、ALP、γ-GT、TBIL及TBA均升高,血气分析中PaO2降低,PA-aO2增大,与Sham组相比均有显著差异(P<0.01),且病理检查CBDL5w组大鼠的肝脏组织可见胆汁性肝纤维化表现,肺组织可见肺毛细血管扩张、充血,证实HPS大鼠模型制成;同时与Sham组相比,CBDL5w组大鼠血清NO及ET-1浓度均升高(P<0.01),肝脏毛细血管血流量降低(P<0.01),肺脏毛细血管血流量增大(P<0.01)。经高压氧治疗后,HBOT1w组大鼠与CBDL5w组相比,以上指标均好转(P<0.01)。HBOT2w组大鼠与CBDL5w组相比,除血清NO水平和肺脏毛细血管血流量无统计学差异(P>0.05)外,其余指标的差异有显著性意义(P<0.01)。结论高压氧治疗大鼠HPS可通过降低血清NO、ET-1浓度,提高组织氧含量及改善肝、肺微循环等,有效改善肝、肺功能及病理,且治疗前期效果更好。

Objective To investigate the therapeutic effects of hyperbaric oxygen （HBO） on hepatopulmonary syndrome （HPS）. Methods The HPS model of SD rats was established by common bile duct ligation （CBDL） A total of 44 SD male rats were radomly divided into 4 groups： 8 rats in the sham operated group （sham）, 12 rats in model group CBDL5w）, 12 rats in the HBO treated for 1 week group （HBOT1w）, and 12 rats in the HBO treated for 2 weeks group （HBOT2w） The rats of two treatment groups accepted hyperbaric oxygen treatment for 1 and 2 weeks respectively after the HPS models established successfully. Then blood gas analysis, liver function, serum NO, ET-1 concentrations were detected, pathohistological examinations of lung and liver were performed and microcirculations of lung and liver were measured by Laser Doppler Perfusion Monitor. Results Comparing with sham operated control group ALT, AST, ALP, γ-GT, TBIL and TBA levers in liver function of CBDL5w group increased （ P 〈 0.01）, ALB and PaO2 decreased（ P 〈 0. 01 ）, PA-aO2 increased （ P 〈 0. 01 ）. The bile canaliculi proliferation and hepatic fibrosis induced by cholestasis could be seen in the liver tissues of CBDL5w group rats pathology, and telangiectasis and congestion in lung tissues. It proved that HPS rats＇ models had been established. In addition, the concentrations of serum NO, ET-1 increased in CBDL5w group （ P 〈 0. 01 ）, liver priming volume decreased （ P 〈 0.01） but increased in lung （ P 〈 0.01） comparing with that in control group. Comparing with CBDL5w group, liver functions of HBOT1w group were improved （ P 〈 0.01 ）, PaO2 increased （ P 〈 0.01 ）, PA-aO2 decreased （ P 〈 0.01 ）, the concentrations of serum NO, ET-1 decreased （ P 〈 0. 01 ）, liver priming volume increased （ P 〈 0. 01 ）, the lung priming volume decreased （ P 〈 0.01）, and the pathology were improved. Comparing with CBDL5w group, the above tested indexes of HBOT2w group were further improved （ P 〈 0.01）, except that the concentrations of serum NO and lung priming volume were not of statistic significance （ P 〉 0.05）. Conclusion The therapy of hyperbaric oxygen in rats with HPS shows benefits to recovery of the liver and lung function and pathology by decreasing the concentration of serum NO, ET-1, increasing the tissues oxygen content and normalizing the microcirculation of lung and liver. Moreover, the therapy in early course of the disease is more effective.