盐酸氨溴索预先给药对内毒素诱导大鼠急性肺损伤的作用  

The effects of pretreatment with ambroxol on endotoxin-induced acute lung injury in rats

作　　者：李立斌[1] 蔡洪流[2] 方强[2] 李利[2] 

机构地区：[1]浙江大学医学院附属第二医院ICU,杭州市310009 [2]浙江大学医学院附属第一医院ICU,杭州市310009

出　　处：《中华麻醉学杂志》2006年第7期655-658,共4页Chinese Journal of Anesthesiology

摘　　要：目的探讨盐酸氨溴索(AMB)预先给药对内毒素(LPS)诱导大鼠急性肺损伤(ALI)的作用及其机制。方法雄性SD大鼠108只,体重196～273 g,12-14周龄。随机分为6组(n=18),A组生理盐水(NS)0．5 ml腹腔注射(i．p．)1 h后,再i．p．NS 0．5 ml;B组i．p．AMB 10 mg／kg 1 h后i．p．NS 0．5 ml;C组i．p．NS 0．5 ml 1 h后i．p．IPS 5 mg／kg;D、E、F组分别i．p．AMB 5、10、20 mg／kg后1 h i．p．LPS 5 mg／kg。i．p．NS(A、B组)或LPS(C、D、E、F组)后1、2、4 h各处死5只大鼠,采用双夹心抗体酶联吸附免疫法测定支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和巨噬细胞炎性蛋白-2(MIP-2)浓度,蛋白印迹法检测肺组织细胞胞浆中磷酸化/非磷酸化c-Jun氨基末端激酶(JNK)的表达。另外3只i．p．NS(A、B组)或LPS(C、D、E、F组)后4 h观察大鼠肺组织形态学变化。结果与A组比较,C、D、E、F组BALF中TNF-α、IL-1β和MIP-2升高;与C组比较,E、F组上述三指标均降低。与A组比较,C、D、E、F组磷酸化JNK表达增多;与C组比较,E、F组磷酸化JNK表达减少,D、E、F组非磷酸化JNK表达增多(P<0．05或0．01)。AMP预先给药可减轻i．p．LPS诱导的肺组织损伤。结论AMB预先给药可减轻LPS诱导大鼠ALI,其机制与抑制肺组织JNK的活化、下调TNF-α、IL-1β和MIP-2的表达有关,且呈剂量依赖性。Objective To study the effects of pretreatment with ambroxol （AMB） on endotoxin （LPS）- induced acute lung injury （ALI） in rats and assess the possible mechanism. Methods One hundred and eight male SD rats aged 12-14 weeks weighing 196-273 g were randomly divided into 6 groups （ n = 18 each） ： group A received intraperitoneal （IP） normal saline （NS） ; group B received AMB 10 mg·kg^-1 IP; group C received LPS 5 mg·kg^-1 IP; group D, E, F received AMB 5 （D）, 10 （E） or 20 （F）mg·kg^-1 IP one hour before IP LPS 5 mg·kg^-1. The animals were killed at 1, 2 and 4h after IP LPS （n = 5 each） for determination of TNF-α, IL-1β and macrophage inflammatory protein-2 （MIR-2） concentration in broncho-alveolar lavage fluid （BALF） and activity of c-Jun-N-terminal kinase （JNK） in lung tissue （western blot）. Another 3 animals in each group were killed at 4h after IP LPS for microscopic examination of lung tissue. Results The TNF-α, IL-1β and MIP-2 concentrations in BALF and the JNK activity in the lung tissue were significantly increased by IP LPS in group C, D, E, F and were significantly attenuated by AMB pretreatment in a dose-dependent manner in group E and F. The damage to the lung tissue produced by IP LPS was significantly ameliorated by AMB pretreatment. Conclusion AMB pretreatment can protect the lungs against the LPS induced acute injury by inhibiting JNK activity and downregulating the expression of TNF-α, IL-1β and MIP-2 in a dose-dependent manner.

关 键 词：氨溴索 内毒素血症 呼吸窘迫综合征 成人 

分 类 号：R563[医药卫生—呼吸系统] R963[医药卫生—内科学]