大剂量盐酸氨溴索对大鼠内毒素性肺损伤保护作用的实验研究

Protective effects of large-dose mucosulvan to lipopolysaccharide-induced lung injury in rats

目的观察大剂量盐酸氨溴索(ambroxol,AMB)对内毒素(LPS)诱导的大鼠急性肺损伤时炎症介质的影响,探讨其对肺脏的保护机制。方法健康雄性SD大鼠随机分成A、B、C、D组,各组分别设立1、2、4 h三个亚组。A组为对照组,B组经腹腔注射AMB,C组经腹腔注射LPS,D组在腹腔注射LPS前1 h经腹腔注射AMB。在到达各时间点后,作肺泡灌洗。测定肺泡灌洗液(BALF)中的肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)与巨噬细胞炎性蛋白-2(M IP-2)。并测定BALF中的乳酸脱氢酶(LDH)与总蛋白量。结果BALF中的LDH和总蛋白量,以及TNF-α、IL-1β与M IP-2等在A组和B组中的差异均无统计学意义(P>0.05),各相同时间点之间差异也无统计学意义(P>0.05);C、D组与A、B组比较各项指标均明显升高(P<0.05),其中以C组升高最明显(P<0.05),D组在各相同时间点均低于C组(P<0.05)。C、D组的LDH与TNF-α在2 h时达到峰值,而总蛋白量、IL-1β、M IP-2在4 h时达到峰值。结论大剂量AMB可降低炎症介质水平,对肺脏具有保护作用。

Objective To study the protective effects of large - dose mucosulvan to lipopolysaccharide（LPS） - induced lung injury in rats. Method Sixty S - D rats were randomly divided into 4 groups （ group A, B, C and D）, and each group divided into 3 subgroups at 1,2 and 4 hours. Group A was control, group B received AMB （20mg/kg） by intraperitoneally injection, group C received LPS （5mg/kg） by intraperitoneally injection, and group D received AMB 1 hour before LPS by intraperitoneally injection respectively. All the animals were killed and collected broncho - alveolar lavage fluid （ BALF ） at 1, 2 and 4 hours respectively. The concentration of LDH and total protein were measured in BALF. The concentration of tumor necrosis factor - α（ TNF - α ）, interleukin - 1β （ IL - 1β）, and macrophage inflammatory protein - 2 （ MIP - 2） werealso monitored in BALF used by ELISA. Results There were no significant differences in the concentration of LDH, total protein, TNF - α, IL - 1β and MIP - 2 between group A and B （ P 〉 0.05 ）. These parameters were significantly higher in group C and D than that of them in group A and B （ P 〈 0.05 ）, but significantly lower in group D than that of them in group C respectively （ P 〈 0.05 ）. LDH and TNF - α at the peak in group C and D at 2 hours, but total protein, IL - 1β and MIP - 2 at the peak at 4 hours respectively. Conclusion Large - dose AMB could protect LPS - induced lung injury through inhibiting inflammatory mediators.