汉防己甲素对大肠杆菌脂多糖致急性肺损伤大鼠肺微血管通透性的影响

Effects of Tetrandrine on Pulmonary Capillary Permeability in Rats with Acute Lung Injury Induced by Lipopolysaccharide

目的探讨汉防己甲素(Tet)对大肠杆菌脂多糖(LPS)所致急性肺损伤(ALI)大鼠肺微血管通透性的影响。方法将健康雄性Wistar大鼠32只,随机分为4组:即正常组、模型组、Tet预防组和Tet治疗组,除正常组外,其他3组采用大肠杆菌LPS静脉注射造成急性肺损伤模型,Tet预防组和Tet治疗组分别于注射LPS前后30min内缓慢静脉注射Tet注射液(20mg/kg),正常组给予等量生理盐水。于初始(0)、0.5、2、4、6h5个时间点采集动脉血测定PaO2和PaCO2,实验结束时测定肺湿重/干重比值(W/D)、支气管肺泡灌洗液(BALF)中性粒细胞百分比;ELISA法测定外周血及BALF中炎症介质TNF-α浓度,采用硫代巴比妥酸比色法测定肺下叶匀浆丙二醛(MDA)含量,取肺上叶行组织病理学检查及肺损伤评分。结果Tet预防组0.5、2、4、6h,Tet治疗组2、4、6hPaO2高于模型组(P<0.05);两Tet组肺泡灌洗液中TNF-α、MDA含量、W/D比值、肺损伤评分和BALF中性粒细胞百分比均低于模型组(P<0.05)。光镜检查显示两Tet组肺脏病理改变较模型组均有所改善。结论Tet对内毒素所致急性肺损伤大鼠有保护作用。

Objective To observe the effects of tetrandrine （Tet） on the pulmonary capillary permeability in rats with acute lung injury induced by intravenous injection of lipopolysaccharide （LPS）, Methods Thirty- two healthy male Wistar rats were randomly divided into 4 groups： the model group, the normal group, the Tet prevention group and the Tet treatment group, 8 in each group. All rats except those in the normal group, were established into acute lung injury model by intravenous injection of LPS. Intravenous injection of Tet （20 rag/ kg） were given to the Tet prevention group 30 min before and to the Tet treatment group 30 min after modeling respectively, and equal volume of normal saline was given to the other two groups instead. Arterial blood sam- ples were collected to determine PaO2 and PaCO2 at the time points of immediately after modeling （0 h）, 0.5 h, 2 h, 4 h, 6 h. The animals were sacrificed by the end of the experiment, the wet/dry weight ratio of lung （W/ D）, neutrophil percentage in bronchoalveolar lavage fluid （BALF）, concentration of TNF-a in peripheral blood and BALF by ELISA, and content of malonaldehyde （MDA） in lobus inferior pulmonis homogenate by thio bar- bituric acid colorimetric method were determined. Pathological change of the upper lobe of lung was examined and lung injury was scored as well. Results As compared with that in the model group, the level of PaO2 was higher in Tet prevention group at 0.5 h, 2 h, 4 h, 6 h and in the Tet treatment group at 2 h, 4 h, 6 h （P〈 0.05） ; and the content of TNF-a, MDA and neutrophil percentage in BALF, as well as W/D and lung injury score were lower in the Tet prevention group and the Tet treatment group （P 〈 0.05）. Pathological changes of lung in the two Tet groups were all better than those in the model group. Conclusion Early intervention with tetrandrine shows a protectiv effect on rats against acute lung injury induced by intravenous injection of LPS