Inhibition of autophagy ameliorates pulmonary microvascular dilation and PMVECs excessive proliferation in rat experimental hepatopulmonary syndrome.
Inhibition of autophagy ameliorates pulmonary microvascular dilation and PMVECs excessive proliferation in rat experimental hepatopulmonary syndrome.
复制标题
抑制自噬可改善大鼠实验性肝肺综合征中的肺微血管扩张和 PMVEC 过度增殖
DOI：
10.1038/srep30833
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发表时间：
2016-08-02
影响因子：
4.6
通讯作者：
Lu K
中科院分区：
文献类型：
--
作者：
Xu D;Chen B;Gu J;Chen L;Belguise K;Wang X;Yi B;Lu K
肝肺综合征(HPS)是一种以肺微血管大量扩张和肺微血管内皮细胞(PMVECs)过度增殖为特征的肝脏缺陷性肺血管病变。越来越多的证据表明，自噬与肺部疾病有关，无论是保护性的还是有害的。因此，探索自噬是否可能参与HPS并在其中起关键作用是非常有趣和重要的。在本研究中，我们报道了胆总管结扎(CBDL)大鼠和体外培养的肺PMVECs在体外HPS模型中被激活的自噬作用。此外，3-甲基腺嘌呤(3-MA)抑制自噬可显著减轻CBDL大鼠体内HPS的病理改变和典型症状，并持续地抑制CBDL大鼠血清诱导的PMVEC体外过度增殖。3-MA介导的这些变化可能解释了体内观察到的肺外观、水肿、微血管扩张和动脉血氧分压显著改善的原因。综上所述，这些结果表明自噬激活可能在HPS的发病机制中发挥关键作用，抑制自噬可能对这种疾病具有治疗潜力。
Hepatopulmonary syndrome (HPS) is a defective liver-induced pulmonary vascular disorder with massive pulmonary microvascular dilation and excessive proliferation of pulmonary microvascular endothelial cells (PMVECs). Growing evidence suggests that autophagy is involved in pulmonary diseases, protectively or detrimentally. Thus, it is interesting and important to explore whether autophagy might be involved in and critical in HPS. In the present study, we report that autophagy was activated in common bile duct ligation (CBDL) rats and cultured pulmonary PMVECs induced by CBDL rat serum, two acceptedin vivoandin vitroexperimental models of HPS. Furthermore, pharmacological inhibition of autophagy with 3-methyladenine (3-MA) significantly alleviated pathological alterations and typical symptom of HPS in CBDL ratsin vivoand consistently 3-MA significantly attenuated the CBDL rat serum-induced excessive proliferation of PMVECsin vitro. All these changes mediated by 3-MA might explain the observed prominent improvement of pulmonary appearance, edema, microvascular dilatation and arterial oxygenationin vivo. Collectively, these results suggest that autophagy activation may play a critical role in the pathogenesis of HPS and autophagy inhibition may have a therapeutic potential for this disease.