肺表面活性物质对急性肺损伤大鼠生存率的影响

Effect of pulmonary surfactant on survival rate of the rats with acute lung injury

目的观察急性肺损伤（ALI）大鼠早期补充肺表面活性物质（PS）对大鼠生存率的影响。方法建立细菌感染导致肺内源性ALI动物模型，并分两步进行：（1）建立大鼠ALI模型，经气管滴入大肠杆菌液[3ml／kg，（4．4-5．6）×10^9 CFU／ml]，动态观察72h大鼠病情演变（n=24）和模型稳定性；并将100h划分为5个连续时间段：第1时间段（正常大鼠，n=11），第2～5时间段分别为感染后0～6h（n=10）、7～18h（n=14）、19～52h（n=87）、53-100h（n=34），观察机械通气15min（n=156）后血气、胸肺有效动态顺应性、肺病理改变情况。（2）大鼠感染后3～6h，PS组（n=16）和NS（n=16）组分别经气管滴入肺表面活性物质或生理盐水，观察生存率。结果（1）本模型较稳定，PaO2／FiO2可从正常（533±16）mmHg（1mmHg=0．133kPa）降到（175±121）mmHg。在第4时间段肺大体标本呈现明显肝样变和弥漫性出血、坏死灶；肺组织切片见肺泡壁明显水肿，大量炎症细胞浸润，严重实变、肺透明膜形成。（2）PS组生存率（26．7％）较NS组（12．5％）明显提高（Log Rank P=0．014，Breslow P=0．0028）。结论在ALI早期补充PS可以延长大肠杆菌致肺内源性ALI大鼠生存时间，提高生存率。

Objective To investigate the effect of pulmonary surfactant supplement on the survival of rats with acute lung injury （ALI）/ARDS during the early stage. Methods We devided the procedure to establish the ALI/ARDS rat mode/infected by Escherichia coli （E. coli） into two sections. Section 1 ： We established an ALI/ARDS rat mode/ through transtracheal application with 3 rnl/kg E. coli of suspended fluid [ （4.4 - 5.6） × 10^9 CFU·ml^-1 ]. First, the disease progress of infected rats for 72 hours （ n = 24 ） and the model stability was observed. Second, we divided the following 100 h into five time segments （n = 156）. The 1st time segment （healthy rats, n = 11 ）, the 2nd time segment to the 5th time segment was respectively during infected 0- 6 h （ n = 10）, 7- 18 h （ n = 14）, 19 - 52 h （ n = 87）, 53 - 100 h （ n = 34）. Peak inspiratory pressures （PIP）, tidal volumes （Vt）, dynamic lung-thorax compliance （Cdyn）, and blcod gas determinations （ PaO2, PaCO2, pH） were recorded after ventilation for 15 minutes under the protocol. Then left lungs morphological observation of three rats in each segment were done to inspect the disease. Section 2 ： survival rates were determined at 72 h for the group PS [n = 16, 1.25 ml/kg CurosurfR（80 mg/ml）] and group NS （n = 16）. Results （1） The rat mode/could be repeated well. PaO2/FiO2 was decreased from normal （533 ± 16） mm Hg to （175 ± 121） mm Hg. At the 4th time segment the infected lungs became hepatized obviously with profuse hemorrhage and necrosis. Under the microscope, a lot of effusion and obvious edema in alveolar wall, granuloeyrie infiltrates in alveoli and interstitia, severe alveolar atelectasis, hyaline membranes m many areas could be seen. （2） The survival rate in group PS （26.7%） was signifficant higher than that in group NS （12.5%） （Log Rank P = 0. 014, Breslow P = 0.002 8）. Conclusion It suggests that supplementary PS at the early stage of ALI can prolong survival time and improve survival rate of the model rats.