汉防己甲素对大肠杆菌脂多糖所致急性肺损伤大鼠炎症介质的影响

目的 探讨中药单体汉防己甲素(trandrine,Tet)干预对静脉注射内毒素(LPS)所致急性肺损伤(ALI)的影响及其可能机制.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30 min内缓慢注射T注射液(20 mg/kg),正常组给予等量生理盐水.于初始(0)、0.5、2,4、6 h 5个时间点采集动脉血测定动脉血氧分压(PaO2)和动脉血二氧化碳分压(PaCO2).实验结束时测定肺组织湿干重比(W/D),检测支气管肺泡灌洗液(BALF)白细胞总数及总蛋白含量;ELISA法测定外周血及BALF中炎症介质TNF-α及BALF中IL-1β、IL-6浓度;测定肺组织一氧化氮(NO)浓度.结论 模型组在LPS输注完毕后PaO2逐渐下降,PaCO2逐渐下降(P<0.05),Tet预防组0.5、2、4、6 h,Tet治疗组2、4、6 h PaO2高于模型组(P<0.05),PaCO2与模型组差异无统计学意义(P<0.05);模型组肺组织W/D值和NO含量、BALF中自细胞计数、总蛋白含量、IL-1β、TNF-α、IL-6浓度显著性增高(P<0.05),两T组均能减轻上述变化(P<0.05).结论 Tet早期干预能减轻内毒素所致急性肺损伤的炎症介质失衡.

Effect of tetrandrine on mediators of inflammation in rats with acute lung injury induced by lipopolysaccharide

Objective To observe the protective effect of tetrandrine pretreatment on rats with acute lung injury induced by intravenous injection of lipopolysaccharide (LPS) and its possible mechanism. Methods Thirty-two healthy male Wistar rats were divided randomly into 4 groups: the model group, the normal group,the Tet precaution group,the Tet treatment group. Eight rats in each group. All rats except those in normal group, were established into acute lung injury model by intravenous injection of LPS. Intravenous injection of Tet (20 mg/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 group instead. Arterial blood samples were collected to determine PaO_2 and PaCO_2 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 ratios of lung (W/D),total leucocyte, total protein and TNF-α levels in bronchoalveolar lavage fluid ( BALF), concentration of IL-1β, TNF-α and IL-6 in peripheral blood and concentration of NO were determined. Results PaO_2 and PaCO_2 decreased significantly after endo-toxin infusion in the model group ( P < 0.05 ). Compared with that in the model group, the level of PaO_2 was higher in Tet prevention group at 0. 5h,2h,4h,6h and in the Tet treatment group at 2 h, 4 h, 6 h, but there was no statistical significance in level of PaCO_2 of three groups (P >0.05) ;and the leucocyte, total protein, the contents of IL-lβ, TNF-α and IL-6 in BALF, as well as W/D and NO of lung were increased significantly (P<0.05) , Tet attenuated these changes. Conclusion Early intervention of tetrandrine can improve disbalance of mediators of inflammation.