Li Jiyu, Li Chun, Subedi Utsab, Subedi Pushpa, Panchatcharam Manikandan, Sun Hong
Department of Cellular Biology and Anatomy, LSU Health Shreveport, Shreveport, LA 71103, USA.
Cells. 2024 Dec 5;13(23):2007. doi: 10.3390/cells13232007.
Light alcohol consumption (LAC) may reduce the incidence and improve the prognosis of ischemic stroke. Recently, we found that LAC promotes cerebral angiogenesis and inhibits early inflammation following ischemic stroke. In addition, LAC upregulates lipocalin-type prostaglandin D2 synthase (L-PGDS) in the brain. Thus, we determined the role of endothelial L-PGDS in the protective effect of LAC. In in vitro studies, chronic exposure to low-concentration ethanol upregulated L-PGDS and significantly increased the proliferation in cultured C57BL/6J mouse brain microvascular endothelial cells (MBMVECs). AT-56, a selective L-PGDS inhibitor, abolished low-concentration ethanol exposure-induced proliferation. In in vivo studies, 8-week gavage feeding with 0.7 g/kg/day ethanol, defined as LAC, promoted cerebral angiogenesis under physiological conditions and following ischemic stroke in male C57BL/6J mice. In addition, LAC inhibited the post-ischemic expression of adhesion molecules, neutrophil infiltration, and microglial activation. AT-56 and endothelial cell (EC)-specific L-PGDS conditional knockout did not significantly alter cerebral angiogenesis and post-ischemic inflammation in the control mice but eliminated the pro-angiogenic and anti-inflammatory effects of LAC. Furthermore, EC-specific L-PGDS conditional knockout alleviated the neuroprotective effect of LAC against cerebral ischemia/reperfusion injury. These findings suggest that endothelial L-PGDS may be crucial in the pro-angiogenic and anti-inflammatory effects of LAC against ischemic stroke.
轻度饮酒（LAC）可能会降低缺血性中风的发病率并改善其预后。最近，我们发现LAC可促进脑缺血后的血管生成并抑制早期炎症。此外，LAC可上调大脑中的脂质运载蛋白型前列腺素D2合酶（L-PGDS）。因此，我们确定了内皮细胞L-PGDS在LAC保护作用中的作用。在体外研究中，长期暴露于低浓度乙醇可上调L-PGDS，并显著增加培养的C57BL/6J小鼠脑微血管内皮细胞（MBMVECs）的增殖。选择性L-PGDS抑制剂AT-56可消除低浓度乙醇暴露诱导的增殖。在体内研究中，以0.7 g/kg/天的乙醇进行为期8周的灌胃喂养（定义为LAC），可促进雄性C57BL/6J小鼠在生理条件下以及脑缺血后的脑微血管生成。此外，LAC可抑制缺血后黏附分子的表达、中性粒细胞浸润和小胶质细胞活化。AT-56和内皮细胞（EC）特异性L-PGDS条件性敲除在对照小鼠中并未显著改变脑微血管生成和缺血后炎症，但消除了LAC的促血管生成和抗炎作用。此外, EC特异性L-PGDS条件性敲除减轻了LAC对脑缺血/再灌注损伤的神经保护作用。这些发现表明，内皮细胞L-PGDS可能在LAC对缺血性中风的促血管生成和抗炎作用中起关键作用。
