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气管内全氟化碳预处理在急性肺损伤实验兔的实验研究

The Experimental Study of Perfluorocarbon Pretreatment Intratracheally in Rabbit Model of Acute Lung Injury

【作者】 刘瑾

【导师】 余革;

【作者基本信息】 广州医学院 , 麻醉学, 2011, 硕士

【摘要】 目的探讨全氟化碳(PFC)汽化吸入预处理对油酸型兔急性肺损伤(ALI)的干预作用。方法实验兔12只随机分为对照组(C组)和PFC预处理组(P组)(n=6)。两组动物麻醉、建立人工气道和动物监测操作完成后,机械通气30min,待动物呼吸、循环指标平稳后(T1),测定相应监测指标为基础值。C组先机械通气60min,再静脉注射油酸造ALI模型后行机械通气120min;P组先经气管内汽化吸入PFC60min,再静脉注射油酸造ALI模型后行机械通气120min。于机械通气(C组)/PFC汽化吸入(P组)60min (T2)、ALI造模成功时(T3)、ALI后30min(T4)、60min(T5)、90min(T6)、120min(T7)各时点记录吸气压峰值、呼气末二氧化碳分压、动脉血气分析、心率、平均动脉压和中心静脉压测定值,并计算肺泡-动脉血氧分压差、肺系数。T7后抽取静脉血样本静置后离心取上清测定TNF-α、IL-1β的含量;深麻醉下处死动物后分离左右肺,对左肺进行肺灌洗留取支气管肺泡灌洗液测定TNF-α、IL-1β的含量,留取右肺作病理检查并统计肺叶不同分区病理损伤评分。应用酶联免疫吸附法(ELISA)检测TNF-α、IL-1β的含量。结果1 P组在T3至T7各时点的吸气压峰值均低于C组(P<0.05)。氧合指数在P组与C组的T3至T7各时点比较分别是130.79±3.65、118.40±2.35、104.04±5.00、96.62±3.14、86.52±3.42 vs 103.26±4.15、95.92±1.92、87.66±3.88、84.43±2.00、77.75±4.58。P组在T3至T7各时点的动脉血氧分压与C组比较明显升高(P<0.05)。P组肺泡-动脉血氧分压差从T3到T6均显著低于C组的对应时点值(P<0.05),在T7两组的肺泡-动脉血氧分压差无显著性差异。P组SaO2值从T3至T7与相应时点C组比较,均升高显著(P<0.05)。P组在T3至T7各时点的动脉血二氧化碳分压与C组比较明显降低(P<0.05),两组测定值(mmHg)分别是39.57±2.08、40.73±0.47、41.72±2.75、42.91±1.99、44.61±1.59 vs 44.39±2.53、46.60±2.31、49.52±3.98、52.03±2.92、54.54±2.39。P组的pH值从T3至T7一直显著高于C组(P<0.05)。P组的HCO3-从T3至T7各时点与C组比较,均显著升高(P<0.05)。P组BE从T3至T7各时点与C组比较,均显著升高(P<0.05)。但P组在心率、平均动脉压和中心静脉压指标与C组比较无显著性差异(P<0.05)。2 P组的肺系数显著低于C组(P<0.05)。P组的兔肺组织病理损伤明显轻于C组,出血、水肿、炎性细胞渗出较少,P组上、中、下叶腹侧和背侧的积分值均显著低于C组(P<0.05)。3 P组的血清、支气管肺泡灌洗液中的TNF-α、IL-1β含量均显著低于C组(P<0.05)。结论1通过建立气道内小剂量PFC给药途径,证实汽化吸入PFC预处理干预可减轻实验兔ALI的严重程度。2以2mL/(kg·h)汽化吸入PFC预处理60min,可改善油酸导致的ALI实验兔呼吸功能及氧合状况,但对血流动力学指标无明显改善。3以2mL/(kg·h)汽化吸入PFC预处理60min,可减轻油酸导致的ALI实验兔肺组织病理损伤,减少炎性因子TNF-α和IL-1β的浸润。PFC干预效果和机制还需进一步验证和研究。

【Abstract】 ObjectiveTo assess the intervention effects of intratracheal administration with vaporized perfluorocarbon(PFC) pretreatment in rabbits of oleic acid(OA)-induced acute lung injury(ALI).MethodsTwelve New Zealand rabbits were randomly divided into control group(group C) and PFC pretreatment group(group P)(n=6 each). After all the rabbits were anesthetized and intubated with mechanical ventilation, and animal monitoring operation were finished, a period of 30min was allowed for animals to stabilize. Baseline measurements were then obtained(T1). In group C, the rabbits were ventilated for 60min and then ALI model was induced by OA. In group P, vaporized perfluorocarbon was given intratracheally for 60min before OA administration. After ALI model was established by OA, the rabbits in two groups were mechanically ventilated for 120min. Peak inspiratory pressure(PIP), expiration carbon dioxide pressure(PETCO2), blood gas analysis, heart rate(HR), mean arterial pressure(MAP) and central venous pressure(CVP) were measured in mechanical ventilation(group C)/PFC pretreatment(group P) for 60min(T2), in T3 that when ALI was established and in time points after ALI 30min(T4), 60min(T5), 90min(T6),120min(T7). AaDO2 and lung coefficient were calculated. After T7, the samples of the venous blood were obtained for measuring concentration of TNF-αand IL-1β. The animals were executed under deep anesthetization, then their left lung and right lung were separated. Bronchoalveolar lavage fluid(BALF) was obtained by lavaging the left lung for detecting the contents of TNF-αand IL-1β. The right lung was obtained for pathological examination and counting the pathological injury scores of different regions of lung lobe.The contents of TNF-αand IL-1βwere detection by the method of enzyme linked immunosorbent assay(ELISA).Results1 PIP in group P significantly was lower than that in group C from T3 to T7 (P<0.05). Oxygenation index in group P and group C from T3 to T7 separately were 130.79±3.65、118.40±2.35、104.04±5.00、96.62±3.14、86.52±3.42 vs. 103.26±4.15、95.92±1.92、87.66±3.88、84.43±2.00、77.75±4.58. PaO2 in group P significantly was higher than that in group C(P<0.05) from T3 to T7. AaDO2 in group P significantly was lower than that in group C from T3 to T6(P<0.05) except T7. SaO2 in group P significantly was higher than that in group C(P<0.05) from T3 to T7. PaCO2 in group P significantly was lower than that in group C(P<0.05) from T3 to T7, and two groups separately were (39.57±2.08)mmHg、(40.73±0.47)mmHg、(41.72±2.75)mmHg、(42.91±1.99)mmHg、(44.61±1.59)mmHg vs. (44.39±2.53)mmHg、(46.60±2.31) mmHg、(49.52±3.98)mmHg、(52.03±2.92)mmHg、(54.54±2.39)mmHg. On arterial blood gas, pH in group P significantly was higher than that in group C(P<0.05) from T3 to T7. HCO3- in group P significantly was higher than that in group C(P<0.05) from T3 to T7. BE in group P significantly was higher than that in group C(P<0.05) from T3 to T7. However, HR, MAP and CVP in group P had no significantly difference comparing with group C.2 Lung coefficient in group P significantly was lower than that in group C (P<0.05). Compared with group C, lung pathological injury was lighter and heamorrhage, edema and effusion of inflammatory factor were fewer in group P. The scores of upper and lower in every lung lobe in group P were significantly inferior to those in group C(P<0.05).3 The concentration of TNF-αand IL-1βin blood serum and BALF in group P were significantly lower than that in group C(P<0.05).Conclusion1 By low-dose PFC administration intratracheally, it was demonstrated that vaporized PFC pretreatment intratracheally was effective to reducing the level of ALI in the rabbits.2 Vaporized PFC pretreatment intratracheally for 60min with the rate of 2mL/(kg·h) can improve the values of respiratory function and oxygenation without adverse effect on hemodynamics in rabbits of OA-induced ALI.3 Vaporized PFC pretreatment intratracheally for 60min with the rate of 2mL/(kg·h) can lighten the lung pathological injury and reduce the release of TNF-αand IL-1βin rabbits of OA-induced ALI. The intervention effects and mechanism of PFC pretreatment will be studied further.

  • 【网络出版投稿人】 广州医学院
  • 【网络出版年期】2012年 05期
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