脂氧素A4调控mRNA-29b保护脂多糖诱导大鼠急性肺损伤的机制研究

Lipoxygenin A4 regulates miRNA-29b to protect rats from LPS-induced acute lung injury

目的探讨脂氧素A4(LXA4)调控miRNA-29家族分子保护脂多糖(LPS)诱导大鼠急性肺损伤(特征性表现为急性呼吸窘迫综合征)的机制。方法将30只SD大鼠按随机数字表法分为LPS组(按20mg/kg尾静脉注射LPS)、LPS+LXA4组(按20mg/kg尾静脉注射LPS 6h后,再按2μg/kg尾静脉注射LXA4作用2h)和对照组(予等量0.9%氯化钠注射液),每组10只。麻醉处死大鼠取肺,左肺用于HE染色和ELISA法检测促炎因子(TNF-α、IL-6)水平,右肺用于RT-PCR法检测miRNA-29家族表达水平。结果 LPS组大鼠肺组织切片可见明显的炎症改变,肺损伤评分及肺组织内TNF-α、IL-6水平较对照组均明显升高(均P<0.05)。LPS+LXA4组大鼠肺组织切片可见炎症反应减轻,肺损伤评分及肺组织内TNF-α、IL-6水平较LPS组均明显下降(均P<0. 05)。RT-PCR结果显示,LPS组大鼠肺组织内miRNA-29a、miRNA-29b表达水平均明显升高(均P<0. 05),LPS+LXA4组miRNA-29b表达水平明显下降(P<0.05)。结论 miRNA-29a、miRNA-29b可能在LPS诱导的大鼠急性肺损伤炎症发生过程中起着调节作用,LPS可能通过下调miRNA-29b表达来发挥促炎症消退的作用。

Objective To investigate the effect of lipoxygenin A4(LXA4) on protecting rats from LPS-induced acute lung injury and its mechanism. Methods Thirty SD rats were randomly divided into three groups with 10 animals in each group. The acute lung injury was induced by caudal vein injection of LPS(20mg/ml) in LPS and LPS+LXA4 groups, and normal saline was injected in control group. The rats in LPS+LXA4 group were challenged with LXA4(2μg/kg) by caudal vein injection, and saline was used in LPS group. After 2h of LXA4 injection, the left lung tissues were harvested for HE and ELISA examination, and the right lung tissues for measuring miRNA-29a,miRNA-29b and miRNA-29c expression. Results Compared with the control group, lung tissue slices in the LPS group showed a significant inflammatory response with infiltrating inflammatory cells and the level of TNF-α and IL-6 increased significantly, while the treatment with LXA4 reduced the inflammatory response. RT-PCR showed that the expression of miRNA-29a and miRNA-29b increased in LPS group, and the expression of miRNA-29b was decreased after LXA4 treatment. Conclusion LXA4 may attenuate LPS-induced lung injury through regulating miRNA-29b expression in rats.