N-乙酰半胱氨酸对烟雾吸入大鼠急性肺损伤的疗效观察

观察N-乙酰半胱氨酸对烟雾吸入所致大鼠急性肺损伤的治疗效果。方法 将健康雄性大鼠108只随机分为空白对照组、损伤对照组、NAC低、中、高剂量组、阳性对照组，每组各18只。除空白对照组外其余各组均制作烟雾吸入性急性肺损伤模型。NAC低、中、高剂量组分别于伤后2 h给予大鼠腹腔注射NAC 100、200、300 mg/kg，阳性对照组于伤后2 h给予大鼠腹腔注射地塞米松10 mg/kg，损伤对照组模型成功后不予处理。比较6组大鼠血气分析情况，采用免疫组化法检测大鼠肺组织NF-kB（p56）及IkB-α的活性，放射免疫分析法测定大鼠肺组织匀浆中TNF-α及IL-6的含量，计算大鼠肺系数和肺湿干重比。光镜下观察大鼠肺组织病理改变、透射电子显微镜观察肺组织亚细胞结构改变。结果 血气分析结果显示，NAC低、中、高剂量组及阳性对照组与损伤对照组比较，各指标差异均有统计学意义（P＜0.05），其中PaO2，SaO2及BE值均上升，PaCO2，HCO3-下降（P＜0.05）；NAC低、中、高剂量组和阳性对照组与损伤对照组比较，肺组织TNF-α及IL-6的含量下降，差异有统计学意义（P＜0.05）；NAC低、中、高剂量组、阳性对照组与损伤对照组比较，PWI和W/D均下降，差异有统计学意义（P＜0.05）；NAC低、中、高剂量组、阳性对照组与损伤对照组相比，NF-kB（p56）在细胞核及胞浆中的阳性反应减弱，差异有统计学意义（P＜0.05）；损伤对照组与空白对照组相比，IkB-α呈强阳性免疫反应，阳性免疫反应产物分布在阳性细胞的胞浆中，差异有统计学意义（P＜0.05）。NAC低、中、高剂量组、阳性对照组与损伤对照组相比，IkB-α在胞浆中的阳性反应减弱，差异有统计学意义（P＜0.05）。结论 N-乙酰半胱氨酸对大鼠烟雾吸入所致急性肺损有保护作用，能够减轻大鼠肺水肿及炎症反应。

Experimental Study on the Therapeutic Effects of N-Acetylcysteine on Smoke Inhalation-induced Acute Lung Injury in Rats

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.