Dl-3-n-Butylphthalide Promotes Remyelination and Suppresses Inflammation by Regulating AMPK/SIRT1 and STAT3/NF-κB Signaling in Chronic Cerebral Hypoperfusion
Dl-3-n-Butylphthalide Promotes Remyelination and Suppresses Inflammation by Regulating AMPK/SIRT1 and STAT3/NF-κB Signaling in Chronic Cerebral Hypoperfusion
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DOI：
10.3389/fnagi.2020.00137
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发表时间：
2020-06-09
影响因子：
4.8
通讯作者：
Lv, Peiyuan
中科院分区：
文献类型：
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作者：
Li, Meixi;Meng, Nan;Lv, Peiyuan
血管性痴呆(VD)的脱髓鞘病变部分归因于慢性脑低灌注(CCH)引起的炎症反应。再髓鞘形成通过诱导少突胶质前体细胞的增殖和分化来促进认知功能障碍的恢复。此前有报道称，DL-3-正丁基苯酞(NBP)可促进认知功能的改善。然而，NBP是否能刺激CCH后的髓鞘再生和抑制炎症仍不清楚。为了回答这个问题，本研究观察了NBP对双侧颈动脉结扎建立的CCH模型大鼠再髓鞘形成的影响。用Morris水迷宫(MWM)检测功能恢复情况，用免疫组织化学和组织学方法检测髓鞘完整性、成熟少突胶质细胞再生和星形胶质细胞增殖抑制情况。免疫印迹法检测5‘AMP激活蛋白激酶(AMPK)/Sirtuin(SIRT)1和信号转导与转录激活因子(STAT)3/核因子-kappaB信号通路的激活情况。结果表明，NBP治疗改善了CCH大鼠的学习记忆能力，并伴随着髓鞘完整性和少突胶质细胞再生增加，星形胶质细胞增殖和炎症减轻。此外，NBP可诱导AMPK/SIRT1信号通路的激活，同时抑制STAT3/NF-kappa B通路。提示NBP通过调节AMPK/SIRT1和STAT3/NF-kappaB信号通路，促进脑出血后再髓鞘形成，抑制炎症反应，从而减轻脑出血后的认知功能障碍。
Demyelination in vascular dementia (VD) is partly attributable to inflammation induced by chronic cerebral hypoperfusion (CCH). Remyelination contributes to the recovery of cognitive impairment by inducing the proliferation and differentiation of oligodendrocyte progenitor cells. It was previously reported that Dl-3-n-butylphthalide (NBP) promotes cognitive improvement. However, whether NBP can stimulate remyelination and suppress inflammation after CCH remains unclear. To answer this question, the present study investigated the effects of NBP on remyelination in a rat model of CCH established by bilateral carotid artery occlusion. Functional recovery was evaluated with the Morris water maze (MWM) test, and myelin integrity, regeneration of mature oligodendrocytes, and inhibition of astrocyte proliferation were assessed by immunohistochemistry and histologic analysis. Additionally, activation of 5 ' AMP-activated protein kinase (AMPK)/Sirtuin (SIRT)1 and Signal transducer and activator of transcription (STAT)3/nuclear factor (NF)-kappa B signaling pathways was evaluated by western blotting. The results showed that NBP treatment improved memory and learning performance in CCH rats, which was accompanied by increased myelin integrity and oligodendrocyte regeneration, and reduced astrocyte proliferation and inflammation. Additionally, NBP induced the activation of AMPK/SIRT1 signaling while inhibiting the STAT3/NF-kappa B pathway. These results indicate that NBP alleviates cognitive impairment following CCH by promoting remyelination and suppressing inflammationviamodulation of AMPK/SIRT1 and STAT3/NF-kappa B signaling.