枸杞多糖通过Akt/eNOS通路减轻LPS致ARDS小鼠肺损伤

摘要

Aim To investigate the effects of Lycium barbarum polysaccharide ( LBP ) on LPS-induced ARDS in mice and the potential mechanisms. Methods Thirty-two C57BL/6 male mice were randomly divided into control group, LPS group, LBP group and LY294002 ( Akt inhibitor) group, with eight mice in each group. The pathological changes in lung tissues were evaluated by HE staining, pulmonary edema was measured by wet/dry ratio( W/D) , and the concentra-tions of total protein and the levels of inflammatory cy-tokines in BALF were determined. MDA and SOD lev-els in lung tissues and the apoptosis of lung tissues were detected. The protein expression levels of cleaved caspase-3, p-Akt and p-eNOS were determined by Western blot. Results Compared with control group, severe pathological lung injury changes were observed in LPS group, and the W/D ratio, levels of total pro-tein and inflammatory cytokines in BALF, levels of MDA in lung tissues and the expression of cleaved caspase-3 significantly increased(P<0.05), while the lung SOD activity, the p-Akt and p-eNOS expression decreased( P<0.05) . LBP could significantly attenu-ate the indexes above(P<0.05). However, the pro-tective effects of LBP on ARDS were inhibited by Akt inhibitor LY294002. Conclusions LBP protects a-gainst LPS-induced ARDS in mice by alleviating EC barrier dysfunction via the suppression of inflamma-tion, oxidative stress and apoptosis, at least partially via activation of the Akt/eNOS singaling pathway.%目的 探讨枸杞多糖( Lycium barbarum polysaccharide, LBP)对LPS致小鼠急性呼吸窘迫综合征( acute respiratory distress syndrome, ARDS)的作用及可能机制.方法 32 只♂C57BL/6 小鼠随机分为对照组、 LPS 组、 LBP 组和LY294002组(Akt抑制剂),每组8只. HE染色观察肺组织病理改变;肺湿干比(W/D)检测肺水肿情况;检测小鼠肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中蛋白浓度及炎性因子水平;检测肺组织MDA、SOD水平及肺组织细胞凋亡情况;Western blot法检测肺组织cleaved caspase-3蛋白、Akt及eNOS磷酸化水平.结果 与对照组相比,LPS组肺组织损伤明显,W/D值、BALF中蛋白含量和炎性因子水平、肺组织中MDA 水平及 cleaved caspase-3 表达明显增高( P <0.05),而肺组织SOD活性、Akt及eNOS磷酸化水平明显下调(P<0.05);LBP能明显改善上述变化(P<0.05);而Akt抑制剂LY294002 能阻断 LBP的作用( P <0.05).结论LBP可抑制肺部炎症反应、减轻氧化应激及减少细胞凋亡,从而缓解ARDS肺微血管内皮屏障损伤,其作用机制可能与Akt/eNOS信号通路激活有关.