Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury
Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury
复制标题
DOI：
10.1186/s13041-020-00601-9
复制
发表时间：
2020-04-22
期刊：
影响因子：
3.6
通讯作者：
Wan, Qi
中科院分区：
文献类型：
--
作者：
Chen, Song-Feng;Pan, Meng-Xian;Wan, Qi
神经炎症是缺血性中风后的一种继发性反应。精氨酸是一种非必需氨基酸，已被证明可以抑制急性炎症反应。在本研究中，我们发现精氨酸治疗减少了大鼠脑缺血/再灌注(I/R)损伤后神经元的死亡，并促进了卒中动物的功能恢复。我们还表明，精氨酸抑制OGD损伤后缺血脑组织和培养的小胶质细胞中的炎症反应。我们进一步提供的证据表明，大鼠I/R损伤后HIF-1α和LDHA水平升高，精氨酸治疗可阻止I/R损伤后HIF-1α和LDHA水平的升高。精氨酸通过抑制缺氧缺血脑组织和培养的小胶质细胞中的HIF-1α和LDHA来抑制炎症反应，并通过减轻HIF-1α/LDHA介导的炎症反应来保护大鼠I/R损伤后的缺血神经元死亡。综上所述，这些结果提示精氨酸诱导的神经保护作用可能是通过抑制HIF-1α/LDHA介导的脑缺血损伤后小胶质细胞的炎症反应实现的。
Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1 alpha and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1 alpha and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1 alpha and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1 alpha/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1 alpha/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.