CAJ | 학술논문

目的探讨机械通气动态通气参数对ARDS犬肺内肺炎症介质的影响及其作用途径.方法取36条健康杂种犬,采用气管内盐酸吸入法建立ARDS模型,随机(随机数字法)分为对照组,ARDS模型组及实验犬组,实验犬组随机分成A,B,c,D四组,每组6条.A组:小潮气量(6 mL/kg),低吸气流速[6mL/kg·s)],高通气频率(30次/min);B组:大潮气量(20mL/kg),高吸气流速[20mL/(kg·s)],高通气频率(30次/min);C组:大潮气量(20 mL/kg),高吸气流速[17 mL/(kg·s)],低通气频率(15次/min);D组:大潮气量(20 mL/kg),低吸气流速[10 mL/(kg·s)],低通气频率(15次/min).机械通气4 h后处死动物,留取肺组织标本行免疫组化、Western blotting检测TNF-α,IL-8,p38 MAPK蛋白的变化,RT-PCR测定TNF-α,IL-8 mRNA的表达,流式细胞仪检测NF-κB活性.结果 B组IL-8蛋白表达明显较A,D组高,c组IL-8蛋白表达较B组有下降趋势,但B,C组之间差异无统计学意义;B组TNF-α的灰度比值明显较其他组高(P<0.01),但与C组比较差异无统计学意义(P>0.05);B组p38 MAPK表达明显较A,D组高(P<0.01);A,D组之间的p38 NAPK表达差异无统计学意义(P>0.05).B组NF-κB p65(33.56±2.85)%表达较A(10.35±0.6)%,D(7.11±0.47)%两组差异有统计学意义,B组与C组(30.87±1.16)%之间差异无统计学意义.结论在相同的大潮气量基础上,高吸气流速和高通气频率可以激活肺组织p38 MAPK及NF-κB通道,炎症介质的释放增加,导致呼吸机相关性肺损伤,小潮气量机械通气可减轻炎症反应.
목적 탐토궤계통기동태통기삼수대ARDS견폐내폐염증개질적영향급기작용도경.방법 취36조건강잡충견,채용기관내염산흡입법건립ARDS모형,수궤(수궤수자법)분위대조조,ARDS모형조급실험견조,실험견조수궤분성A,B,c,D사조,매조6조.A조:소조기량(6 mL/kg),저흡기류속[6mL/kg·s)],고통기빈솔(30차/min);B조:대조기량(20mL/kg),고흡기류속[20mL/(kg·s)],고통기빈솔(30차/min);C조:대조기량(20 mL/kg),고흡기류속[17 mL/(kg·s)],저통기빈솔(15차/min);D조:대조기량(20 mL/kg),저흡기류속[10 mL/(kg·s)],저통기빈솔(15차/min).궤계통기4 h후처사동물,류취폐조직표본행면역조화、Western blotting검측TNF-α,IL-8,p38 MAPK단백적변화,RT-PCR측정TNF-α,IL-8 mRNA적표체,류식세포의검측NF-κB활성.결과 B조IL-8단백표체명현교A,D조고,c조IL-8단백표체교B조유하강추세,단B,C조지간차이무통계학의의;B조TNF-α적회도비치명현교기타조고(P<0.01),단여C조비교차이무통계학의의(P>0.05);B조p38 MAPK표체명현교A,D조고(P<0.01);A,D조지간적p38 NAPK표체차이무통계학의의(P>0.05).B조NF-κB p65(33.56±2.85)%표체교A(10.35±0.6)%,D(7.11±0.47)%량조차이유통계학의의,B조여C조(30.87±1.16)%지간차이무통계학의의.결론 재상동적대조기량기출상,고흡기류속화고통기빈솔가이격활폐조직p38 MAPK급NF-κB통도,염증개질적석방증가,도치호흡궤상관성폐손상,소조기량궤계통기가감경염증반응.
Objective To evaluate the effect on inflammatory mediators and mechanism of dynamic factors on lung injury in a dog model of acute respiratory distress syndrome (ARDS). Method The ARDS dog model was duplicated by instillation hydrochloric acid. The dogs were randomly (random number) divided into six groups: (1) normal control group (N group); (2) ARDS group (M group); (3) low VT (6 mL/kg) at respiratory rate 30, low inspiratory flow 6 mL/(kg·s). (4) large VT (20 mL/kg) at respiratory rate 30, high inspiratory flow 20 mL/kg·s.(5) large VT (20 mL/kg) at respiratory rate 15, high inspiratory flow 17 mL/(kg·s). (6) large VT (20 mL/kg) at respiratory rate 15, low inspiratory flow 10 mL/(kg·s). All the dogs were killed after 4 h ventilation. TNF-α、IL-8, p38 MAPK and NF-κB activity in the lung were measured. Results The expression of IL-8 protein in B and C groups was much higher than that of other groups ( P < 0.01) . There was no significant difference among M, A and D groups (P > 0.05). The gray scale ratio of B group was obviously higher than that of other groups (P < 0.01), except C group (P > 0.05). There was no significant changes among M, A and D groups in TNF-α protein contents. p38 MAPK value of positive staining of B group was the strongest, significantlyhigher than that of D group ( P < 0.01) .The expression of p38 MAPK in B and C groups was much higher than other groups (P <0.01). NF-κB activity in B group (33.56±2.85%) was significantly higher than that in A (10.35±0.6%)、D(7. 11 ± 0.47%)group, but there was no difference between B and C group (30.87 ± 1.16%). Conclusions Ventilation at high tidal volume, high inspiratory flow rate, high respiratory rate could activate p38 MAPK and increase the activity of NF-κB with the result of aggravating the release of inflammatory mediators. p38 MAPK and NF-κB activation are the major mechanisms in the development of VILI.