中华结核和呼吸杂志
中華結覈和呼吸雜誌
중화결핵화호흡잡지
Chinese Journal of Tuberculosis and Respiratory Diseases
2010年
8期
587-592
,共6页
张隽%童朝晖%秦志强%庞宝森%牛淑洁%王辰
張雋%童朝暉%秦誌彊%龐寶森%牛淑潔%王辰
장준%동조휘%진지강%방보삼%우숙길%왕신
呼吸,人工%呼吸窘迫综合征,成人%转录因子AP-1%细胞黏附分子%白细胞介素10
呼吸,人工%呼吸窘迫綜閤徵,成人%轉錄因子AP-1%細胞黏附分子%白細胞介素10
호흡,인공%호흡군박종합정,성인%전록인자AP-1%세포점부분자%백세포개소10
Respiration,artificial%Respiratory distress syndrome,adult%Transcription factor AP-1%Cell adhesion molecules%Interleukin-10
目的 研究呼吸机相关肺损伤(VILI)兔细胞间黏附分子-1(ICAM-1)、白细胞介素(IL)-10的表达及激活蛋白-1(AP-1)DNA结合活性的变化,并探讨其在VILI炎症反应中的意义.方法 应用40 ml/kg的大潮气量(VT)机械通气建立兔VILI模型.将40只新西兰兔按随机数字表法分为非机械通气对照组、常规VT组、大VT 1h组、大VT 2 h组及大VT 4 h组.用酶联免疫吸附法(ELISA)检测肺组织匀浆可溶性细胞间黏附分子-1(sICAM-1)和IL-10含量,逆转录多聚酶链反应(RT-PCR)检测mRNA表达.凝胶电泳迁移率分析法(EMSA)测定AP-1的活性,同时测定PaO2、髓过氧化物酶(MPO)、肺湿重/干重比值(W/D).结果 (1)肺组织匀浆中sICAM-1含量:大VT2 h组[(23±5)ng/L]及大VT 4 h组[(35±5)ng/L]均高于常规VT组[(16±4)ng/L],均P＜0.05;大VT4 h组高于大VT 1 h组[(19±4)ng/L]及大VT 2 h组(均P＜0.01).肺组织匀浆IL-10含量:大VT2 h组[(24±4)ng/L]和大VT4 h组[(26±5)ng/L]均高于常规VT组[(15±2)ng/L,均P＜0.05],大VT4 h组高于大VT 1 h组[(19±4)ng/L,P＜0.05].ICAM-1 mRNA含量:大VT 2 h组(1.18±0.19)及大VT4 h组(1.29±0.19)均高于常规VT组(0.84±0.13,均P＜0.05).大VT4 h组高于大VT1 h组(0.96±0.24,P＜0.05).IL-10 mRNA含量:大VT 4 h组(1.13±0.17)高于常规VT组(0.84±0.20)和大VT 1 h组(0.86±0.12,均P＜0.05).(2)AP-1的DNA结合活性:大VT 2 h组(34±8)和大VT4 h组(38±9)均高于常规VT组(23±9,均P＜0.01),大VT4 h组高于大VT 1 h组(25±9,P＜0.01).(3)病理学检查显示大VT机械通气后随时间延长肺损伤逐渐加重,大VT机械通气2 h可见MPO升高,4 h可见PaO2下降及W/D升高.结论 ICAM-1、IL-10参与了VILI的炎症反应过程,二者升高可能与其mRNA的表达增高有关.核转录因子AP-1可能参与了上述炎性介质基因的转录调节.
目的 研究呼吸機相關肺損傷(VILI)兔細胞間黏附分子-1(ICAM-1)、白細胞介素(IL)-10的錶達及激活蛋白-1(AP-1)DNA結閤活性的變化,併探討其在VILI炎癥反應中的意義.方法 應用40 ml/kg的大潮氣量(VT)機械通氣建立兔VILI模型.將40隻新西蘭兔按隨機數字錶法分為非機械通氣對照組、常規VT組、大VT 1h組、大VT 2 h組及大VT 4 h組.用酶聯免疫吸附法(ELISA)檢測肺組織勻漿可溶性細胞間黏附分子-1(sICAM-1)和IL-10含量,逆轉錄多聚酶鏈反應(RT-PCR)檢測mRNA錶達.凝膠電泳遷移率分析法(EMSA)測定AP-1的活性,同時測定PaO2、髓過氧化物酶(MPO)、肺濕重/榦重比值(W/D).結果 (1)肺組織勻漿中sICAM-1含量:大VT2 h組[(23±5)ng/L]及大VT 4 h組[(35±5)ng/L]均高于常規VT組[(16±4)ng/L],均P＜0.05;大VT4 h組高于大VT 1 h組[(19±4)ng/L]及大VT 2 h組(均P＜0.01).肺組織勻漿IL-10含量:大VT2 h組[(24±4)ng/L]和大VT4 h組[(26±5)ng/L]均高于常規VT組[(15±2)ng/L,均P＜0.05],大VT4 h組高于大VT 1 h組[(19±4)ng/L,P＜0.05].ICAM-1 mRNA含量:大VT 2 h組(1.18±0.19)及大VT4 h組(1.29±0.19)均高于常規VT組(0.84±0.13,均P＜0.05).大VT4 h組高于大VT1 h組(0.96±0.24,P＜0.05).IL-10 mRNA含量:大VT 4 h組(1.13±0.17)高于常規VT組(0.84±0.20)和大VT 1 h組(0.86±0.12,均P＜0.05).(2)AP-1的DNA結閤活性:大VT 2 h組(34±8)和大VT4 h組(38±9)均高于常規VT組(23±9,均P＜0.01),大VT4 h組高于大VT 1 h組(25±9,P＜0.01).(3)病理學檢查顯示大VT機械通氣後隨時間延長肺損傷逐漸加重,大VT機械通氣2 h可見MPO升高,4 h可見PaO2下降及W/D升高.結論 ICAM-1、IL-10參與瞭VILI的炎癥反應過程,二者升高可能與其mRNA的錶達增高有關.覈轉錄因子AP-1可能參與瞭上述炎性介質基因的轉錄調節.
목적 연구호흡궤상관폐손상(VILI)토세포간점부분자-1(ICAM-1)、백세포개소(IL)-10적표체급격활단백-1(AP-1)DNA결합활성적변화,병탐토기재VILI염증반응중적의의.방법 응용40 ml/kg적대조기량(VT)궤계통기건립토VILI모형.장40지신서란토안수궤수자표법분위비궤계통기대조조、상규VT조、대VT 1h조、대VT 2 h조급대VT 4 h조.용매련면역흡부법(ELISA)검측폐조직균장가용성세포간점부분자-1(sICAM-1)화IL-10함량,역전록다취매련반응(RT-PCR)검측mRNA표체.응효전영천이솔분석법(EMSA)측정AP-1적활성,동시측정PaO2、수과양화물매(MPO)、폐습중/간중비치(W/D).결과 (1)폐조직균장중sICAM-1함량:대VT2 h조[(23±5)ng/L]급대VT 4 h조[(35±5)ng/L]균고우상규VT조[(16±4)ng/L],균P＜0.05;대VT4 h조고우대VT 1 h조[(19±4)ng/L]급대VT 2 h조(균P＜0.01).폐조직균장IL-10함량:대VT2 h조[(24±4)ng/L]화대VT4 h조[(26±5)ng/L]균고우상규VT조[(15±2)ng/L,균P＜0.05],대VT4 h조고우대VT 1 h조[(19±4)ng/L,P＜0.05].ICAM-1 mRNA함량:대VT 2 h조(1.18±0.19)급대VT4 h조(1.29±0.19)균고우상규VT조(0.84±0.13,균P＜0.05).대VT4 h조고우대VT1 h조(0.96±0.24,P＜0.05).IL-10 mRNA함량:대VT 4 h조(1.13±0.17)고우상규VT조(0.84±0.20)화대VT 1 h조(0.86±0.12,균P＜0.05).(2)AP-1적DNA결합활성:대VT 2 h조(34±8)화대VT4 h조(38±9)균고우상규VT조(23±9,균P＜0.01),대VT4 h조고우대VT 1 h조(25±9,P＜0.01).(3)병이학검사현시대VT궤계통기후수시간연장폐손상축점가중,대VT궤계통기2 h가견MPO승고,4 h가견PaO2하강급W/D승고.결론 ICAM-1、IL-10삼여료VILI적염증반응과정,이자승고가능여기mRNA적표체증고유관.핵전록인자AP-1가능삼여료상술염성개질기인적전록조절.
Objective To study the expression of intercelluler cell adhesion molecule-1 (ICAM-1) , Interleukin-10(1L-10)and the activation of transcription factor activator protein-1 (AP-1 )in a rabbit model of ventilator-induced lung injury ( VILJ) and therefore to explore their possible role in VILI. Methods The VILI model was established by mechanical ventilation with a large tide volum (VT ) of 40 ml/kg. Forty healthy male New Zealand rabbits were randomly divided into 5 groups: a control group without mechanical ventilation, a conventional ventilation group, and injurious ventilation with large VT for 1 h group, 2 h group and 4 h group. The concentrations of soluble ICAM-1 ( sICAM-1 ) and IL-10 in lung homogenates were measured by enzyme-linked immunosorbent assay ( ELISA) . The level of mRNA was measured by semiquantitative transcription-polymerase chain reaction ( RT-PCR). The DNA-binding activity of AP-1 was measured by electrophoretic mobility shift assay ( EMSA). The partial arterial blood pressure of oxygen (PaO2) , myeloperoxidase (MPO) in lung homogenate, wet lung weight to dry lung weight ratio (W/D) were observed. Results (l)The concentrations of sICAM-1 in large VT for 2 h group (23 ±5) ng/L and 4 h group(35 ±5) ng/L were higher than that in the conventional ventilation group( 16 ±4)ng/L(P all < 0. 05) ,and that in the Large VT for 4 h group were higher than that in 1 h group(19 ±4)ng/L and 2 h group (P all < 0.01). The concentrations of IL-10 in the large VT for 2 h group (24 ±4) ng/L and 4 h group(26 ±5) ng/L were higher than that in the conventional ventilation group(15 ±2)ng/L(P all <0. 05) , and that in the Large VT for 4 h group was higher than that in the 1h group( 19 ±4)ng/L(P <0.05). The level of ICAM-1 mRNA in the large VT for 2 h group (1. 18 ± 0. 19) and 4 h group (1. 29 ±0. 19) were higher than that in the conventional ventilation group (0. 84±0. 13)(Pall<0. 05) ,and that in Large VT for 4 h group was higher than that in 1 h group(0. 96 ±0. 24) (P <0. 05). The level of IL-10 mRNA in the large VT for 4 h group (1. 13 ±0. 17) was higher than that in the conventional ventilation group(0. 84 ±0. 20) and Large VT for 1 h group(0. 86 ±0. 12) (P all < 0. 05). (2)The DNA-binding activity of AP-1 in the large VT for 2 h group (33. 77 ± 8. 23) and 4 h group (38 ±9) were higher than that in the conventional ventilation group (23 ±9)(Pall<0. 01) ,and that in Large VT for 4 h group was higher than that in lh group (25 ±9)(P<0. 01). (3) Histopathological findings demonstrated that diffused alveolar damage induced by mechanical ventilation was worse with time, and after mechanical ventilation with large VT for 2 h, the level of MPO began to increase, and for 4 h the PaO2 reduced and the W/D increased . Conclusions ICAM-1 and IL-10 took part in the inflammatory responses of VILI, and their up-regulation maybe due to the increase of their mRNA. Nuclear transcription factor AP-1 maybe involved in the transcriptional regulation mechanisms of these inflammatory mediators.
