CAJ | 학술논문

目的：探讨氯胺酮雾化吸入对呼吸机所致肺损伤（VILI）兔模型的保护作用机制。方法选取48只家兔，按随机数字表法分为自主呼吸组（C组）、呼吸机损伤模型组（V组）、0.9%氯化钠溶液雾化吸入组（NS组）和不同浓度氯胺酮处理组（分别为K1组、K2组和K3组），每组8只。除C组外，其他组均给予大潮气量通气（VT=40ml/kg）4h，K1、K2、K3、NS组在给予大潮气量通气同时间断雾化吸入容量为4ml/（kg·h）、浓度为12.5、25、50mg/ml的氯胺酮或等量0.9%氯化钠溶液（持续10min）。连续监测平均动脉血压（MAP）、心率（HR）及气道峰压（Ppeak）、平台压（Pplat）变化，每间隔1h测定动脉氧分压（PaO2），计算PaO2/FiO2。持续通气4h后测定肺组织中髓过氧化物酶（MPO）及超氧化物歧化酶（SOD）活性和肺表面活性物质相关蛋白（SP- A）水平。结果 C组MAP及HR均较为稳定，V组、K组、NS组内随着通气时间的延长，MAP及HR呈不同程度下降，其中V组、NS组较K组下降更为显著，K组中K3组下降相对较少。C组通气过程中Ppeak、Pplat相对稳定，V组、K组、NS组在通气过程中Ppeak、Pplat均呈上升趋势，其中V组、NS组升高最为显著，与V组同一时点相比，K3组Ppeak、Pplat显著降低（P＜0.05）。C组在整个实验过程中PaO2/FiO2无明显变化，其他各组PaO2/FiO2在呼吸机通气1h后均有所升高，通气2h后开始逐渐下降，通气4h时V组和NS组下降最为明显，K组下降程度比V组和NS组趋缓。通气4h时K1、K2组的PaO2/FiO2高于V组，但无统计学差异（P＞0.05），K3组显著高于V、NS、K1、K2组，差异均有统计学意义（均P＜0.05）。与C组比较，V组和NS组肺组织中SOD活性和SP- A水平降低，MPO活性升高（P＜0.05）。与V组比较，K3组肺组织中SOD活性和SP- A浓度升高，MPO活性降低，且差异均有统计学意义（均P＜0.05）。结论高浓度氯胺酮雾化吸入对机械通气所致兔肺损伤有保护作用，该作用与氯胺酮雾化吸入减少肺表面物质的破坏、改善氧化应激反应有关。目的：探討氯胺酮霧化吸入對呼吸機所緻肺損傷（VILI）兔模型的保護作用機製。方法選取48隻傢兔，按隨機數字錶法分為自主呼吸組（C組）、呼吸機損傷模型組（V組）、0.9%氯化鈉溶液霧化吸入組（NS組）和不同濃度氯胺酮處理組（分彆為K1組、K2組和K3組），每組8隻。除C組外，其他組均給予大潮氣量通氣（VT=40ml/kg）4h，K1、K2、K3、NS組在給予大潮氣量通氣同時間斷霧化吸入容量為4ml/（kg·h）、濃度為12.5、25、50mg/ml的氯胺酮或等量0.9%氯化鈉溶液（持續10min）。連續鑑測平均動脈血壓（MAP）、心率（HR）及氣道峰壓（Ppeak）、平檯壓（Pplat）變化，每間隔1h測定動脈氧分壓（PaO2），計算PaO2/FiO2。持續通氣4h後測定肺組織中髓過氧化物酶（MPO）及超氧化物歧化酶（SOD）活性和肺錶麵活性物質相關蛋白（SP- A）水平。結果 C組MAP及HR均較為穩定，V組、K組、NS組內隨著通氣時間的延長，MAP及HR呈不同程度下降，其中V組、NS組較K組下降更為顯著，K組中K3組下降相對較少。C組通氣過程中Ppeak、Pplat相對穩定，V組、K組、NS組在通氣過程中Ppeak、Pplat均呈上升趨勢，其中V組、NS組升高最為顯著，與V組同一時點相比，K3組Ppeak、Pplat顯著降低（P＜0.05）。C組在整箇實驗過程中PaO2/FiO2無明顯變化，其他各組PaO2/FiO2在呼吸機通氣1h後均有所升高，通氣2h後開始逐漸下降，通氣4h時V組和NS組下降最為明顯，K組下降程度比V組和NS組趨緩。通氣4h時K1、K2組的PaO2/FiO2高于V組，但無統計學差異（P＞0.05），K3組顯著高于V、NS、K1、K2組，差異均有統計學意義（均P＜0.05）。與C組比較，V組和NS組肺組織中SOD活性和SP- A水平降低，MPO活性升高（P＜0.05）。與V組比較，K3組肺組織中SOD活性和SP- A濃度升高，MPO活性降低，且差異均有統計學意義（均P＜0.05）。結論高濃度氯胺酮霧化吸入對機械通氣所緻兔肺損傷有保護作用，該作用與氯胺酮霧化吸入減少肺錶麵物質的破壞、改善氧化應激反應有關。
목적：탐토록알동무화흡입대호흡궤소치폐손상（VILI）토모형적보호작용궤제。방법선취48지가토，안수궤수자표법분위자주호흡조（C조）、호흡궤손상모형조（V조）、0.9%록화납용액무화흡입조（NS조）화불동농도록알동처리조（분별위K1조、K2조화K3조），매조8지。제C조외，기타조균급여대조기량통기（VT=40ml/kg）4h，K1、K2、K3、NS조재급여대조기량통기동시간단무화흡입용량위4ml/（kg·h）、농도위12.5、25、50mg/ml적록알동혹등량0.9%록화납용액（지속10min）。련속감측평균동맥혈압（MAP）、심솔（HR）급기도봉압（Ppeak）、평태압（Pplat）변화，매간격1h측정동맥양분압（PaO2），계산PaO2/FiO2。지속통기4h후측정폐조직중수과양화물매（MPO）급초양화물기화매（SOD）활성화폐표면활성물질상관단백（SP- A）수평。결과 C조MAP급HR균교위은정，V조、K조、NS조내수착통기시간적연장，MAP급HR정불동정도하강，기중V조、NS조교K조하강경위현저，K조중K3조하강상대교소。C조통기과정중Ppeak、Pplat상대은정，V조、K조、NS조재통기과정중Ppeak、Pplat균정상승추세，기중V조、NS조승고최위현저，여V조동일시점상비，K3조Ppeak、Pplat현저강저（P＜0.05）。C조재정개실험과정중PaO2/FiO2무명현변화，기타각조PaO2/FiO2재호흡궤통기1h후균유소승고，통기2h후개시축점하강，통기4h시V조화NS조하강최위명현，K조하강정도비V조화NS조추완。통기4h시K1、K2조적PaO2/FiO2고우V조，단무통계학차이（P＞0.05），K3조현저고우V、NS、K1、K2조，차이균유통계학의의（균P＜0.05）。여C조비교，V조화NS조폐조직중SOD활성화SP- A수평강저，MPO활성승고（P＜0.05）。여V조비교，K3조폐조직중SOD활성화SP- A농도승고，MPO활성강저，차차이균유통계학의의（균P＜0.05）。결론고농도록알동무화흡입대궤계통기소치토폐손상유보호작용，해작용여록알동무화흡입감소폐표면물질적파배、개선양화응격반응유관。
Objective To investigate the protective effect of nebulized inhalation of ketamine on ventilator- induced lung injury in rabbits and its mechanism. Methods Forty eight adult rabbits were randomly divided into six groups with 8 in each group:control group(C), lung injury group(V), normal saline group(NS) and 3 ketamine groups(K1 , K2 , K3). Al rabbits were giv-en large tidal volume ventilation (VT=40mL/kg, respiratory rate 12/min) for 4h except control group. Rabbits in K groups inhaled 4ml/(kg·h) of 12.5mg/ml, 25 mg/ml or 50mg/ml nebulized ketamine for 10 min/h;rabbits in NS group inhaled 4ml/(kg·h) of nebu-lized normal saline for 10min/h. The mean arterial blood pressure (MAP), heart rate (HR), the peak airway pressure (Ppeak) and plateau pressure (Pplat) were continuously monitored, the PaO2/FiO2 value was calculated by measuring the arterial oxygen (PaO2) at intervals of 1h. The lung tissue samples was col ected 4 h after treatment, and the activities of myeloperoxidase (MPO), super-oxide dismutase (SOD) and the surfacant protein A (SP- A) contents in lung tissue were detected. Results The MAP and HR in group C were relatively stable during the experiment, while decreased in group V, group K, group NS with prolonged ventilation. The MAP and HR in group V, group NS decreased more markedly than those in group K;and those in group K3 were decreased least. The Ppeak and Pplat were relatively stable during ventilation, while the indexes in group V, group K and group NS showed an upward trend, and it was the most significant in group V and group NS. Compared to those indexes in group V at the same time points, those is group K3 were significantly lower (P<0.05). The PaO2/FiO2 in group C was not significantly changed during the experience, but it increased 1h after ventilation in other groups, then declined at 2h after ventilation and decreased significantly 4h after ventilated in groups V and NS, the decrease tended to become moderated in the group K than that in groups V and NS. The PaO2/FiO2 was significantly higher in group K3 than that in groups V, NS, K1, K2 4h after ventilation (P<0.05) . Compared with group C, the concentration of MPO was significantly increased in groups V and NS (P<0.05), the activity of SOD and SP- A were significantly decreased(P<0.05). The activity of MPO in group K3 was significantly decreased, while the concentration SP- A and the activity of SOD were increased compared with group V (P<0.05). Conclusion Nebulized ketamine inhalation can attenuate the lung injury induced by ventilator in rabbits, which is probably related to reducing the destruction of pulmonary surfactant sub-stances and improving lung oxidative stress.