脱氢穿心莲内酯琥珀酸半酯上调水通道蛋白5减轻LPS诱导的急性肺损伤肺水肿的实验研究

Dehydroandrographolide succinate attenuates pulmonary edema in LPS-induced acute lung injury through up-regulation of aquaporin-5

目的探讨脱氢穿心莲内酯琥珀酸半酯(DAS)对于急性肺损伤状态下水通道蛋白5(AQP-5)的调节作用及对肺水肿清除的影响。方法 30只雄性BALB/C小鼠平均分为对照组(Control组)、治疗组(LPS+DAS组)和内毒素组(LPS模型组),每组10只。通过HE染色观察肺组织病理学改变;使用湿/干比(W/D)分析肺水肿程度;使用RTPCR和western blotting对AQP-5的表达进行测量。结果小鼠气道内注射内毒素(LPS)72小时后肺损伤评分和W/D比值明显增加,AQP-5表达量水平明显下降,差异有显著统计学意义(均P<0.05)。同时发现,LPS+DAS组小鼠肺损伤评分及W/D比值较LPS组较低,而AQP-5表达量较之升高,差异均有统计学意义(均P<0.05)。结论脱氢穿心莲内酯琥珀酸半酯可以有效减轻LPS诱导的小鼠ALI导致的肺水肿,其机制可能与上调了AQP-5的表达相关。该结果为脱氢穿心莲内酯琥珀酸半酯治疗ALI/ARDS相关的肺水肿奠定了实验基础。

Objective To investigate the therapeutic value of dehydroandrographolide succinate （DAS） on the ex- pression of AQP-5 in LPS-induced acute lung injury in mice. Methods Thirty male BALB/C mice were randomly divided into 3 groups, Control group, LPS-FDAS group and LPS group （n= 10）. HE staining and lung injury score system were used to evaluate the pathological changes in lung. Wet to dry ratio （W/D） was included to measure the degree of lung e- dema. RT-PCR and western blotting were used to measure AQP-5 expression. Results After 72h LPS stimulation, se- vere pathological changes, increased W/D and down-regulated AQP-5 expression were observed. However, compared with LPS group, pathological changes and W/D were significantly ameliorated, meanwhile, AQP-5 expression was markedly up-regulated was notably reduced in LPS-I-DAS group. Conclusion Our results indicated that DAS attenuates oulmonarv edema in LPS-indueed acute lung injury possibly through up-regulation of aquaporin-5.