百草枯致家猪急性肺损伤模型的建立

Reproduction of acute lung injury model induced by paraquat in piglet

目的 建立百草枯（PQ）致家猪急性肺损伤（ALI）模型.方法 将10头健康雌性家猪按随机数字表法分为对照组（n=4）和实验组（n=6）.实验组家猪腹腔注射20％ PQ溶液20 mL制备ALI模型;对照组给予等量生理盐水.用脉搏指示连续心排血量（PiCCO2）监测仪动态监测动物心率（HR）、平均动脉压（MAP）、血管外肺水指数（EV LWI）、肺血管通透性指数（PVPI）,记录动脉血pH值、动脉血氧分压（PaO2）、动脉血二氧化碳分压（PaCO2）、氧合指数（PaOJFiO2）,以及气道峰压（PIP）、气道平台压（Pplat）,每0.5 h测定1次,直到PaOJFiO2≤300 mmHg（1 mmHg=0.133 kPa）.制模成功时显微镜下观察肺组织病理学改变.结果 实验组5头猪成功建立ALI模型,平均制模成功时间为（4.5±0.2）h.实验组染毒后HR、MAP、EVLWI、PVPI、PIP和Pplat均呈上升趋势,制模成功时各指标明显高于对照组[HR（次/min）：132.0±6.9比113.0±3.4,t=-21.632,P=0.000; MAP（mmHg）：114.0±6.0比98.0±3.5,t=-18.217,P=0.000; EVLWI（mUkg）：19.2±2.8比12.5±1.2,t=-76.283,P=0.000; PVPI：5.9±1.3比3.1±0.4,t=-31.879,P=0.000; PIP（cmH2O,1 cmH2O=0.098 kPa）：25.4±2.5比18.6±1.5,t=-77.421,P=0.000;Pplat（cmH2O）：19.6±2.2比13.5±1.7,t=-69.452,P=0.000].实验组染毒后pH值、PaO2及PaO2/FiO2均呈下降趋势,而PaCO2逐渐上升,制模成功时血气分析指标与对照组比较差异均有统计学意义[pH值：7.35±0.04比7.43±0.05,t=9.108,P=0.000; PaO2（mmHg）：82.0±7.4比172.0± 11.6,t=102.470,P=0.000; PaCO2（mmHg）：44.0±4.0比35.0±2.0,t=-10.217,P=0.000; PaOjFiO2（mmHg）：273.0±14.8比573.0±22.5,t=341.565,P=0.000].肺组织病理结果显示,制模成功时肺组织出现明显的损伤性改变.结论 采用腹腔注射20％ PQ溶液20 mL可以建立稳定的PQ致猪ALI模型.

Objective To reproduce acute lung injury （ALI） model induced by paraquat （PQ） in piglet.Methods Ten healthy female piglets were divided into control group （n =4） and the experimental group （n =6） in accordance with the random number table.The experimental group was given intraperitoneal injection of 20％ PQ （20 mL） to reproduce the model of ALI,while the control group was given the same amount of normal saline.All piglets were dynamically monitored with pulse-indicated continuous cardiac output （PiCCO） for heart rate （HR）,mean arterial pressure （MAP）,extravascular lung water index （EVLWI） and pulmonary vascular permeability index （PVPI）.Changes in arterial blood pH,oxygen partial pressure （PaO2）,partial pressure of carbon dioxide （PaCO2）,oxygenation index （PaOJFiO2）,peak inspiratory pressure （PIP） and platform of the airway pressure （Pplat） were recorded until the PaO2/FiO2 ≤ 300 mmHg （1 mmHg=0.133 kPa）.Pathological changes in lung tissue under microscopy were observed.Results Model of ALI induced by PQ was successfully reproduced in the experimental group in 5 piglets.The average time of successful reproduction was （4.5 ±0.2） hours.The HR,MAP,EVLWI,PVPI,PIP and Pplat of the experimental group were increased gradually after PQ intraperitoneal injection,and all indices were significantly higher than those in control group when the model was successfully reproduced [HR （bpm）：132.0 ± 6.9 vs.113.0 ± 3.4,t=-21.632,P=0.000; MAP （mmHg）：114.0 ± 6.0 vs.98.0 ± 3.5,t=-18.217,P=0.000; EVLWI （mL/kg）：19.2 ± 2.8 vs.12.5 ± 1.2,t=-76.283,P=0.000; PVPI：5.9 ± 1.3 vs.3.1 ±0.4,t=-31.879,P=0.000; PIP （cmH2O,1 cmH2O =0.098 kPa）：25.4 ± 2.5 vs.18.6 ± 1.5,t=-77.421,P=0.000 ; Pplat （cmH2O）：19.6 ± 2.2 vs.13.5 ± 1.7,t=-69.452,P=0.000].The pH value,PaO2 and PaO2/FiO2 declined gradually while the PaCO2 elevated gradually in experimental group after PQ intraperitoneal injection,the differences between the two groups were statistically significant [pH value：7.35 ±0.04 vs.7.43 ±0.05,t=9.108,P=0.000; PaO2 （mmHg）：82.0 ±7.4 vs.172.0 ± 11.6,t=102.470,P=0.000; PaCO2 （mmHg）：44.0±4.0 vs.35.0 ±2.0,t=-10.217,P=0.000; PaO2/FiO2 （mmHg）：273.0 ± 14.8 vs.573.0 ± 22.5,t=341.565,P=0.000].Obvious damage of pulmonary tissue was shown when the model was reproduced.Conclusion By intraperitoneal injections of 20％ PQ 20 mL,a stable PQ-induced ALI model can be reproduced in piglets.