Catalpol promotes oligodendrocyte survival and oligodendrocyte progenitor differentiation via the Akt signaling pathway in rats with chronic cerebral hypoperfusion
Catalpol promotes oligodendrocyte survival and oligodendrocyte progenitor differentiation via the Akt signaling pathway in rats with chronic cerebral hypoperfusion
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梓醇通过 Akt 信号通路促进慢性脑灌注不足大鼠少突胶质细胞存活和少突胶质细胞祖细胞分化
DOI：
10.1016/j.brainres.2014.03.001
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发表时间：
2014-04-29
期刊：
影响因子：
2.9
通讯作者：
Li, Hongli
中科院分区：
文献类型：
--
作者：
Cai, Qiyan;Yao, Zhongxiang;Li, Hongli
慢性脑低灌流可导致脑白质损伤(WMLs)，从而导致认知功能障碍。虽然炎症和少突胶质细胞凋亡被认为与WMLs的发病有关，但目前还没有找到有效的治疗方法。本研究通过Akt信号通路，研究环烯醚萜糖苷梓醇能否通过促进少突胶质细胞存活和少突胶质细胞祖细胞分化来减轻WMLs。采用永久性结扎双侧颈总动脉的方法建立大鼠慢性脑低灌注模型。术后每日腹腔注射梓醇(5 mg/kg)或生理盐水，连续10d。术后第30天，缺血区白质炎症、少突胶质细胞凋亡和髓鞘损伤较假手术组明显加重。梓醇治疗可显著抑制脑白质炎症，减轻少突胶质细胞凋亡和髓鞘损伤。梓醇还可显著增加磷酸化Akt(p-Akt)的表达和成熟少突胶质细胞的数量，这些作用可被PI3K抑制剂LY294002逆转。综上所述，梓醇通过Akt信号通路促进少突胶质细胞存活和少突胶质细胞前体分化，从而减轻低灌流诱导的WMLs。我们的结果提示梓醇可能是治疗脑血管WMLs的候选药物。(C)2014爱思唯尔B.V.保留所有权利。
Chronic cerebral hypoperfusion is thought to induce white matter lesions (WMLs), which contribute to cognitive impairment Although inflammation and oligodendrocyte apoptosis are believed to be involved in the pathogenesis of WMLs, effective therapies have not been identified yet. This study investigated whether catalpol, an iridoid glycoside, can alleviate WMLs by promoting oligodendrocyte survival and oligodendrocyte progenitor differentiation via the Akt signaling pathway in rats with chronic cerebral hypoperfusion. A rat model of chronic cerebral hypoperfusion was created through permanent occlusion of bilateral common carotid arteries. Catalpol (5 mg/kg) or saline was intrapeiitoneally administered daily for 10 days following the operation. On the 30th day after surgery, inflammation, oligodendrocyte apoptosis, and myelin damage in the ischemic white matter were more severe and evident than in the sham control group. Treatment with catalpol significantly suppressed white matter inflammation and attenuated oligodendrocyte apoptosis and myelin damage. The expression of phosphorylated Akt (p-Akt) and the number of mature oligodendrocytes were also markedly increased by catalpol treatment, and these effects were reversed by the PI3K inhibitor LY294002. In conclusion, catalpol attenuates hypoperfusion-induced WMLs by promoting oligodendrocyte survival and oligodendrocyte progenitor differentiation through the Akt signaling pathway. Our results suggest that catalpol may be a candidate for treating cerebrovascular WMLs. (C) 2014 Elsevier B.V. All rights reserved.