N—乙酰半胱氨酸對煙霧吸入大鼠急性肺損傷的療效觀察

王文迪 李小兵 劉光晶

摘 要：目的 觀察N-乙酰半胱氨酸對煙霧吸入所致大鼠急性肺損傷的治療效果。方法 將健康雄性大鼠108只隨機分為空白對照組、損傷對照組、NAC低、中、高劑量組、陽性對照組，每組各18只。除空白對照組外其余各組均制作煙霧吸入性急性肺損傷模型。NAC低、中、高劑量組分別于傷后2 h給予大鼠腹腔注射NAC 100、200、300 mg/kg，陽性對照組于傷后2 h給予大鼠腹腔注射地塞米松10 mg/kg，損傷對照組模型成功后不予處理。比較6組大鼠血氣分析情況，采用免疫組化法檢測大鼠肺組織NF-kB（p56）及IkB-α的活性，放射免疫分析法測定大鼠肺組織勻漿中TNF-α及IL-6的含量，計算大鼠肺系數和肺濕干重比。光鏡下觀察大鼠肺組織病理改變、透射電子顯微鏡觀察肺組織亞細胞結構改變。結果 血氣分析結果顯示，NAC低、中、高劑量組及陽性對照組與損傷對照組比較，各指標差異均有統計學意義（P<0.05），其中PaO2，SaO2及BE值均上升，PaCO2，HCO3-下降（P<0.05）；NAC低、中、高劑量組和陽性對照組與損傷對照組比較，肺組織TNF-α及IL-6的含量下降，差異有統計學意義（P<0.05）；NAC低、中、高劑量組、陽性對照組與損傷對照組比較，PWI和W/D均下降，差異有統計學意義（P<0.05）；NAC低、中、高劑量組、陽性對照組與損傷對照組相比，NF-kB（p56）在細胞核及胞漿中的陽性反應減弱，差異有統計學意義（P<0.05）；損傷對照組與空白對照組相比，IkB-α呈強陽性免疫反應，陽性免疫反應產物分布在陽性細胞的胞漿中，差異有統計學意義（P<0.05）。NAC低、中、高劑量組、陽性對照組與損傷對照組相比，IkB-α在胞漿中的陽性反應減弱，差異有統計學意義（P<0.05）。結論 N-乙酰半胱氨酸對大鼠煙霧吸入所致急性肺損有保護作用，能夠減輕大鼠肺水腫及炎癥反應。

關鍵詞：吸入性損傷；乙酰半胱氨酸；肺；腫瘤壞死因子；炎癥反應；地塞米松

中圖分類號：R563 文獻標識碼：A DOI：10.3969/j.issn.1006-1959.2018.23.027

文章編號：1006-1959（2018）23-0101-04

Abstract：Objective To investigate the therapeutic effects of N-Acetylcysteineon smoke inhalation-induced acute lung injury in rats.Methods 108 healthy male rats were randomly divided into control group， injury control group， low， middle and high NAC groups， and positive control group （18 rats in each group）.The model of acute lung injury induced by smoke inhalation was made in all groups except the blank control group.The rats in the low， middle and highNAC groups were given intraperitoneal injection of NAC 50，100，150 mg/kg 2 h after injury. The rats in the control group were given 10 mg/kg of dexamethasone 2 h after injury.The model of injury control group was not treated after successful construction.Comparison of blood gas analysis in 6 groups of rats was made，the activities of NF-kB（p56） and IkB-α in rat lung tissue were detected by immunohistochemical method.The contents of TNF-α and IL-6 in the lung homogenate of rats were measured by radioimmunoassay， and the lung coefficient and lung wet dry weight ratio were calculated.Then the pathological changes of lung tissue were observed under light microscope and the changes of subcellular structure in lung tissue were observed by transmission electron microscope （TEM）.Results The results of blood gas analysis showed that there were significant differences between the low， middle and high doses of NAC and the positive control group compared with the injured control group （P<0.05）.PaO2，SaO2 and BE both increased and PaCO2，HCO3- decreased （P<0.05）.The contents of TNF-α and IL-6 in lung tissue decreased in low， medium and high dose of NAC and positive control group （dexamethasone） compared with the injured control group，the difference was statistically significant （P<0.05）.Compared with the injured control group， PWI and W/D decreased significantly in the low， middle and high dose groups of NAC and the positive control group，the difference was statistically significant （P<0.05）.Compared with the injured control group， the positive reaction of NF-kB（p56） in the nucleus and cytoplasm was decreased in the low， medium and high dose groups of NAC， and the positive reaction in the positive control group was lower than that in the injured control group，the difference was statistically significant （P<0.05）.Compared with the control group， IkB-α showed strong positive immunoreactivity， and the positive immunoreactive products were distributed in the cytoplasm of the positive cells，the difference was statistically significant（P<0.05）.The positive reaction of IkB-α in cytoplasm of the low， middle and high dose groups of NAC and the positive control group was significantly lower than that of the injured control group，the difference was statistically significant（P<0.05）.Conclusion N- acetylcysteine has protective effect on acute lung injury induced by smoke inhalation in rats and can alleviate pulmonary edema and inflammation in rats.

Key words：Inhalation injury；Acetylcysteine；Lung；Tumor necrosis factor；Inflammatory reaction；Dexamethasone

煙霧吸入性損傷常發生于不通風或密閉的環境中，包括熱力損傷和煙霧損傷，熱力損傷主要是吸入大量干熱和濕熱的空氣導致呼吸道、肺實質損傷，煙霧損傷主要是吸入大量炭粒和化學物質，導致呼吸道、肺實質化學性損傷，煙霧吸人性損傷的發病率和病死率都很高[1]。大面積燒傷合并吸入性損傷是指患者發生嚴重燒傷的同時，因吸入有毒煙霧或燒傷性化學物質而導致呼吸道受到化學性損傷，情況嚴重者甚至損傷肺實質。……