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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 investigate the effect of ambroxol hydrochloride (AMB) pretreatment on endotoxin-induced acute lung injury (ALI) in rats and its mechanism. Methods One hundred and eight male Sprague Dawley rats weighing 196-27 3 g and 12-14 weeks of age were enrolled. The rats were randomly divided into 6 groups (n = 18). Group A NS (0.5 ml) was injected intraperitoneally (i.p.) for 1 h, then i. p. NS 0.5 ml; Group B i. p. AMB 10 mg / kg after 1 h i. p. NS 0.5 ml; Group C i. p. NS 0.5 ml after 1 h i. p. IPS 5 mg / kg; D, E, F respectively i. p. AMB 5,10,20 mg / kg after 1 h i. p. LPS 5 mg / kg. i. p. Five rats were sacrificed 1, 2 and 4 h after NS (group A, B) or LPS (group C, D, E and F) respectively. BALF was measured by double sandwich enzyme-linked immunosorbent assay ), TNF-α (TNF-α), interleukin-1β (IL-1β) and macrophage inflammatory protein-2 (MIP-2) were detected by Western blotting. / Not phosphorylated c-Jun N-terminal kinase (JNK) expression. The other three i. p. The morphological changes of lung tissue were observed 4 h after NS (A, B group) or LPS (C, D, E, F group). Results Compared with group A, the levels of TNF-α, IL-1β and MIP-2 in BALF were increased in groups C, D, E and F; compared with group C, the above three indexes in groups E and F were all decreased. Compared with group A, the expression of phosphorylated JNK increased in groups C, D, E and F; compared with group C, the expression of phosphorylated JNK decreased in groups E and F, while the expression of non-phosphorylated JNK increased in groups D, E and F .05 or 0.01). Pre-administration of AMP attenuates i. p. LPS-induced lung injury. CONCLUSION: AMB pretreatment can reduce ALI induced by LPS in rats. The mechanism may be related to inhibiting the activation of JNK, decreasing the expression of TNF-α, IL-1β and MIP-2 in a dose-dependent manner.