应用肝硬化联合腹腔室隔综合征构建新的肝肺综合征大鼠模型研究

A new strategy to establish a hepatopulmonary syndrome model in rats by inducing abdominal compartmentsyndrome in the presence of cirrhosis

目的寻找一种制备肝肺综合征大鼠模型的新方法。方法雄性SD大鼠40只，随机均分为正常对照组（皮下注射橄榄油）、腹腔室隔综合征（ACS）组（皮下注射橄榄油，腹腔内注射琥珀明胶）、肝硬化组（CCl4造模）、模型组（ccl4造模，腹腔内注射琥珀明胶）。进行血气分析与肺组织病理学检测。结果（1）血气分析结果显示：正常对照组、ACS组、肝硬化组、模型组pH值分别为7．41±0．04、7．22±0．06，7．53土0．04、7．47±0．02，组间比较，差异均有统计学意义（P值均〈0．05）。ACS组动脉血氧分压、肺泡一动脉氧压差分别为（58．57±5．41）intoHg、（83．86士28．49）mmHg，模型组分别为（58．20±3．19）mmHg、（84．80土11．82）mmHg，正常对照组分别为（86．67±1．37）mmHg、（38．17±9．20）mmHg，肝硬化组为分别为（85．00土2．53）mmHg、（37．00±6．23）mmHg，组间比较，差异均有统计学意义∽值均〈0．05）。（2）肺组织病理学检测结果显示ACS组肺泡间隔增宽，肺泡腔大小不一，肺容量减少，局部肺泡腔水肿、出血，肺泡壁毛细血管扩张；旰硬化组部分肺泡间隔增厚，肺泡腔大小不一，肺容量减少，炎细胞浸润，局部肺血管内可见充血；模型组肺泡间隔增宽明显，肺泡腔大小不一、有明显的出血，纤维索性渗出，大量炎性细胞浸润，肺容量减少，肺泡壁毛细血管扩张明显，局部增生，巨噬细胞聚集，微血栓形成。结论腹腔内注射琥珀明胶并维持适当的腹压达一定时间可以制备ACS模型；肝硬化联合ACS是建立HPS模型的一种新的方法。

Objective To find a practical method to establish hepatopulmonary syndrome （HPS） in rats for use as an experimental model system. Methods Forty male Sprague-Dawley rats were equally divided into a normal group （injected subcutaneously with 3 m[Jkg of olive oil for 12 weeks）, abdominal compatlment syndrome （ACS） group （injected subcutaneously with 3 mL/kg olive oil for 12 weeks, followed by an intraperitoneal injection of 4% succinylated gelatin and maintanence of 20 mmHg abdominal pressure for 3 h）, cirrhosis group （injected subcutaneously with 40% carbon tetrachloride （CC14） in olive oil twice weeklyfor 12 weeks, with first dose doubled）, and an ACS＋ cirrhosis （HPS model） group （CCh-induced, followed by the inlraperitoneal injection with succinylated gelatin and 3 h of 20 mmHg abdominal pressure）. The mice were sacrificed to perform blood gas analysis and to assess lung pathology. Comparisons between two groups were carried out by non-parametric analysis, and multiple comparisons were carded out by the Kruskal-Wallis H test. Results Blood gas analyses showed significant differences in the values ofpH for the normal group （7.41± 0.04）, the ACS group （7.22±0.06）,the cirrhosis group （7.53 ±0.04）, and the HPS model group （7.47± 0.02） （P〈 0.05）. The ACS group and the HPS model group showed significantly different values of partial pressure of oxygen （PaO2; 58.57± 5.41 and 58.20±3.19 mm Hg） and of alveolar-arterial oxygen difference （AaDO2; 83.86 ±28.49 and 84.80±11.82 mm Hg） than the normal group and the cirrhosis group （PaO2：86.67± 1.37 and 85.00±2.53 mm Hg; AaDO2：38.17 4. 9.20 and 37.00±6.23 mm Hg） （P 〈 0.05）. Pathological analysis of the lungs from the ACS group revealed widened alveolar septa, different-sized alveolar spaces, reduced lung capacity, edema and hemorrhage in some of the alveolar cavities, and telangiectasia in the alveolar walls. The lungs from the cirrhosis group also showed widened alveolar septa, different-sized alveolar spaces, and reduced lung capacity, but were distinct in the features of inflammatory cell infiltration, and hyperemia in the pulmonary vessels. The lungs from the HPS model group showed all of the features of both the lungs from the ACS and cirrhosis groups, but also showed macrophage accumulation and microthrombi in the pulmonary vessels. Concluslun Inducing ACS in the setting of CCL4-induced cirrhosis in a rat generates pathological features that adequately mirror those of HPS and may represent a useful experimental model for in vivo studies of liPS.