發(fā)布時間：2018-08-17 13:34

【摘要】：第一部分：百草枯中毒致家豬急性肺損傷模型的建立 目的： 建立百草枯（paraquat,PQ）致家豬急性肺損傷模型，為進一步研究肺保護性通氣策略治療百草枯中毒提供條件。 方法： 將10頭健康雌性家豬隨機分為對照組（n=4）和實驗組（n=6）。實驗組家豬給予20%PQ溶液20ml腹腔注射，對照組給予等量生理鹽水腹腔注射。使用脈搏指示連續(xù)心排血量（PiCCO）監(jiān)測儀動態(tài)監(jiān)測兩組動物心率（HR）、平均動脈壓（MAP）、血管外肺水指數(shù)（ELWI）、肺血管通透性指數(shù)（PVPI），記錄動脈血pH值、氧分壓（PaO2）、二氧化碳分壓（PaCO2）、氧合指數(shù)（PaO2/FiO2）、氣道峰壓（PIP）及氣道平臺壓（Pplat）變化，直到氧合指數(shù)≤300mmHg。 結果： 實驗組有5頭豬成功建立急性肺損傷模型，平均造模成功時間為（4.5±0.2）h。實驗組從造模開始2.5h后HR、MAP、ELWI、PVPI、PIP和Pplat呈逐漸上升趨勢，造模成功時實驗組與對照組相比差異有統(tǒng)計學意義（均P0.05）。造模開始后實驗組pH值、PaO2及氧合指數(shù)呈逐漸下降趨勢，而PaCO2逐漸上升，造模成功時實驗組與對照組相比差異有統(tǒng)計學意義（均P0.05）。肺組織病理結果顯示造模成功時肺組織出現(xiàn)明顯的損傷性改變。 結論： 本方法可以建立穩(wěn)定的百草枯致急性肺損傷模型，為進一步動物實驗研究提供條件。 第二部分：脈搏指示連續(xù)心排血量監(jiān)測下不同潮氣量機械通氣對百草枯中毒家豬急性肺損傷的影響 目的： 研究脈搏指示連續(xù)心排血量（PiCCO）監(jiān)測下不同潮氣量（VT）聯(lián)合呼氣末正壓（PEEP）機械通氣對百草枯中毒家豬急性肺損傷/急性呼吸窘迫綜合癥（ALI/ARDS）的影響。 方法： 用20%百草枯原液20ml腹腔注射制備家豬急性百草枯中毒后ALI/ARDS模型，造模成功后隨機分為三組，每組各6只。接呼吸機輔助呼吸，潮氣量分別為小VT組（6ml/kg）、中VT組（10ml/kg）和大VT組（15ml/kg），PEEP均設為10cmH2O。采用PiCCO監(jiān)測造模前（基礎值）、造模成功（t0）及機械通氣后2h（t2）、4h（t4）及6h（t6）時的心率（HR）、平均動脈壓（MAP）、血管外肺水指數(shù)（ELWI）和肺血管通透性指數(shù)（PVPI），記錄各時點的動脈血pH值、氧分壓（PaO2）、二氧化碳分壓（PaCO2）以及氣道峰壓（PIP）及氣道平臺壓（Pplat）等指標，計算氧合指數(shù)（PaO2/FiO2）；同時在造模前、造模成功時及機械通氣后6h分別進行肺組織穿刺進行蘇木精-伊紅（HE）染色法觀察肺組織病理變化。 結果： 家豬在注射百草枯后（4.5±0.8）h達到ALI/ARDS。造模成功時各組HR和MAP均較基礎值明顯上升，差異有統(tǒng)計學意義（均P0.05）；機械通氣后各組HR和MAP均逐漸下降，與同組t0相比差異均有統(tǒng)計學意義（均P0.05）。造模成功時各組pH值、PaO2及氧合指數(shù)與基礎值相比均明顯下降，而PaCO2明顯上升，差異均有統(tǒng)計學意義（均P0.05）；機械通氣后各組pH值呈逐漸下降趨勢，通氣后6h小VT組下降最為明顯；通氣后2h各組PaO2及氧合指數(shù)均明顯上升，其中小VT組上升最為明顯，之后均逐漸下降，通氣后6h小VT組PaO2及氧合指數(shù)明顯高于其余兩組；機械通氣后各組PaCO2均呈逐漸上升趨勢，以小VT組上升最為明顯。造模成功時各組ELWI和PVPI與基礎值相比均明顯上升，差異均有統(tǒng)計學意義（均P0.05）；機械通氣后2h各組ELWI均明顯上升，之后小VT組及中VT組ELWI逐漸下降，通氣后6h小VT組下降更為明顯；通氣后各組PVPI無明顯變化。機械通氣后小VT組PIP及Pplat逐漸下降，而中VT組和大VT組則均逐漸上升，通氣后6h小VT組PIP及Pplat明顯低于其余兩組。造模成功時（t0）肺泡組織呈明顯損傷性改變，通氣6h后（t6）損傷加重，其中以大VT組最為明顯，小VT組損傷較輕。 結論： 小潮氣量聯(lián)合呼氣末正壓機械通氣可減輕百草枯中毒急性肺損傷，改善氧合狀況。 第三部分：壓力控制法與呼氣末正壓遞增法肺復張對百草枯致急性肺損傷家豬血流動力學的影響 目的： 探討壓力控制（PC）法與呼氣末正壓（PEEP）遞增法肺復張（RMs）對百草枯（PQ）致急性肺損傷家豬血流動力學的影響。 方法： 10頭健康雌性家豬給予20%PQ溶液20ml腹腔注射建立百草枯中毒急性肺損傷/急性呼吸窘迫綜合癥（ALI/ARDS）模型。建模成功后將所有動物隨機分為壓力控制法肺復張組（RM1）和PEEP遞增法肺復張組（RM2），每組各5頭。比較兩組間正常值（基礎值）、建模成功時（t0）、RMs后5min（t5）、15min（t15）和30min（t30）時的心率（HR）、平均動脈壓（MAP）、心功能指數(shù)（CI）、氧分壓（PaO2）、二氧化碳分壓（PaCO2）、氧合指數(shù)（PaO2/FiO2）變化。同時在造模前、t0及t30時刻分別進行肺組織穿刺進行蘇木精-伊紅（HE）染色并觀察肺組織病理變化。 結果： 造模成功時HR與MAP與基礎值相比均明顯上升，而CI明顯降低（均P0.05），RMs后HR與MAP呈逐漸下降趨勢，，在RMs后5minRM1組HR與MAP明顯低于RM2組（均P0.05），RMs后30min兩組間HR與MAP差異無統(tǒng)計學意義（均P0.05）；CI在RMs后呈先下降后上升的趨勢，RMs復張后5min時RM1組明顯高于RM2組（P0.05），RMs后30min兩組間差異無統(tǒng)計學意義（P0.05）；造模成功時兩組PaO2和氧合指數(shù)均明顯下降，而PaCO2明顯上升（與基礎值相比均P0.05）；RMs后兩組PaO2、PaCO2和氧合指數(shù)均呈上升趨勢，兩組間差異無統(tǒng)計學意義（均P0.05）。RMs后30min兩組動物的肺組織均表現(xiàn)出多樣的病理學改變，主要表現(xiàn)為肺泡上皮細胞脫落、肺泡間隔進一步增寬及肺泡過度膨脹，部分可見肺泡間隔斷裂。 結論： 壓力控制法與呼氣末正壓遞增法肺復張均可以明顯改善百草枯中毒家豬ALI/ARDS時的氧合狀況，而且壓力控制法對血流動力學的影響較小。
[Abstract]:Part one: establishment of acute lung injury model induced by paraquat poisoning in pigs *
Objective:
To establish a model of acute lung injury induced by paraquat (PQ) in pigs, and provide conditions for further study of lung protective ventilation strategy in the treatment of paraquat poisoning.
Method:
Ten healthy female pigs were randomly divided into control group (n=4) and experimental group (n=6). Pigs in experimental group were given 20% PQ solution intraperitoneally, and control group was given the same amount of normal saline intraperitoneally. Pulmonary vascular permeability index (PVPI), arterial blood pH, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), peak airway pressure (PIP) and airway plateau pressure (Pplat) were recorded until the oxygenation index was less than 300 mmHg.
Result:
In the experimental group, 5 pigs were successfully established * an acute lung injury model, and the average time for establishing the model was (4.5 + 0.2) h.. After the start of 2.5h, the HR, MAP, ELWI, PVPI, PIP and Pplat in the experimental group showed a gradual upward trend. When the model was successful, the difference between the experimental group and the control group was statistically significant (P0.05). PaCO2 increased gradually, and the difference between the experimental group and the control group was statistically significant (all P 0.05). The pathological results of lung tissue showed that the lung tissue showed obvious damage changes after successful modeling.
Conclusion:
This method can establish a stable paraquat-induced acute lung injury model and provide conditions for further animal experimental study.
Part 2: Effect of mechanical ventilation with different tidal volume on acute lung injury in pigs poisoned by Paraquat
Objective:
To study the effects of different tidal volume (VT) combined with positive end-expiratory pressure (PEEP) mechanical ventilation on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in pigs poisoned by paraquat.
Method:
ALI/ARDS model of pigs after acute paraquat poisoning was established by intraperitoneal injection of 20% paraquat solution 20 ml. Six pigs in each group were randomly divided into three groups. Heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were recorded at 2 h (t2), 4 h (t4) and 6 h (t6) after mechanical ventilation. The arterial pH, partial oxygen pressure (PaO2), partial carbon dioxide pressure (PaCO2), peak airway pressure (PIP) and plateau pressure (Pplateau) were recorded at each time point. (PaO2/FiO2) puncture and hematoxylin-eosin (HE) staining were used to observe the pathological changes of lung tissue before and 6 hours after mechanical ventilation.
Result:
The HR and MAP of each group were significantly higher than those of the baseline (all P 0.05). After mechanical ventilation, the HR and MAP of each group were gradually decreased, and the difference was statistically significant (all P 0.05). The pH value, PaO2 and oxygenation index and baseline of each group were significantly higher than those of the same group (all P 0.05). Compared with the baseline values, PaCO2 increased significantly, and the difference was statistically significant (all P 0.05); After mechanical ventilation, the pH value of each group showed a gradual downward trend, especially in the small VT group at 6 hours after ventilation; PaO2 and oxygenation index of each group increased significantly at 2 hours after ventilation, especially in the small VT group, and gradually decreased after 6 hours after ventilation. PaO2 and oxygenation index in T group were significantly higher than those in the other two groups; PaCO2 in each group increased gradually after mechanical ventilation, especially in small VT group. After ventilation, the levels of PIP and Pplat in small VT group decreased gradually, while those in medium VT group and large VT group increased gradually. The levels of PIP and Pplat in small VT group were significantly lower than those in the other two groups at 6 hours after ventilation. After 6h ventilation (T6), the injury was aggravated, especially in the large VT group, and in the small VT group.
Conclusion:
Small tidal volume combined with positive end-expiratory pressure mechanical ventilation can alleviate acute lung injury caused by paraquat poisoning and improve oxygenation.
Part III: Effects of pressure control and positive end-expiratory pressure increment on hemodynamics in pigs with paraquat-induced acute lung injury
Objective:
To investigate the effects of pressure control (PC) and positive end-expiratory pressure (PEEP) incremental lung relaxation (RMs) on hemodynamics in pigs with acute lung injury induced by paraquat (PQ).
Method:
10 healthy female pigs were given 20% PQ solution 20 ml intraperitoneal injection to establish acute lung injury/acute respiratory distress syndrome (ALI/ARDS) model of paraquat poisoning. Heart rate (HR), mean arterial pressure (MAP), cardiac function index (CI), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaO2), and oxygenation index (PaO2/FiO2) were measured at 5 min (t5), 15 min (t15) and 30 min (t30) after RMs. Change.
Result:
HR and MAP in RM1 group were significantly lower than those in RM2 group (all P 0.05). HR and MAP in RMs group were significantly lower than those in RM2 group (all P 0.05). HR and MAP in RM1 group were significantly lower than those in RM2 group (all P 0.05). There was no significant difference in HR and MAP between the two groups 30 minutes after RMs (all P 0.05). RM1 group was significantly higher than RM2 group at n time (P 0.05), and there was no significant difference between the two groups at 30 minutes after RMs (P 0.05); PaO2 and oxygenation index were significantly decreased, while PaCO2 was significantly increased (P 0.05 compared with the baseline); PaO2, PaCO2 and oxygenation index were increased in both groups after RMs, and there was no significant difference between the two groups (P 0.05). The alveolar epithelial cells were exfoliated, the alveolar septum was widened and the alveolar septum was overstretched, and some of the alveolar septum was broken.
Conclusion:
Both pressure control and positive end-expiratory pressure incremental lung relaxation could significantly improve oxygenation in paraquat poisoned pigs with ALI/ARDS, and the effect of pressure control on hemodynamics was less.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R595.4

【參考文獻】

相關期刊論文 前1條

1 YIN Yu;GUO Xiang;ZHANG Shou Lin;SUN Cheng Ye;;Analysis of Paraquat Intoxication Epidemic (2002-2011) within China[J];Biomedical and Environmental Sciences;2013年06期

本文編號：2187796