US EPA

8272160 

Journal Article 

NO-cGMP-PKG信号通路在天麻素促进脑缺血后海马神经发生中的作用 

Xiao, H; Ma, XJ; Cheng, OM; Qiu, HM; Jiang, QS 

2019 

1 

Zhongguo Zhongyao Zazhi / China journal of Chinese materia medica
ISSN: 1001-5302 

Zhongguo Zhongyi Yanjiuyuan 

44 

24 

5451-5456 

Chinese 

32237394 

10.19540/j.cnki.cjcmm.20190819.401 

MEDLINE:32237394 

This paper was aimed to investigate the effect of gastrodin (GAS) on hippocampal neurogenesis after cerebral was chemic and to explore its mechanism of action related to NO. The cerebral ischemia model of C57BL/6 mice was established by bilateral common carotid artery occlusion. The pathological changes in hippocampal CA1 region and the cognitive function of mice were assessed by HE staining and Morris water maze test, respectively. The count of BrdU/NeuN positive cells in dentate gyrus was detected by immunofluorescence assay. The NOS activity and the NO content were determined by colorimetric and nitrate reduction methods, respectively. The level of cGMP was measured by ELISA kit, and the PKG protein expression was tested by Western blot. On postoperative day 8, the hippocampal CA1 pyramidal neurons of mice showed irregular structure, with obvious nuclear pyknosis, loose cell arrangement and obvious decrease in the number of neurons. On postoperative day 29, the spatial learning ability and memory were decreased. These results indicated cerebral ischemia in mice. Meanwhile, the BrdU/NeuN positive cells were increased significantly in ischemic mice, indicating that neurogenesis occurred in hippocampus after cerebral ischemia. Treatment with different doses of gastrodin (50 and 100 mg•kg-1) significantly ameliorated the pathological damages in the CA1 region, improved the ability of learning and memory, and promoted hippocampal neurogenesis. At the same time, both the NOS activity and the NO concentration were decreased in model group, but the cGMP level was increased, and the PKG protein expression was up-regulated. Gastrodin administration activated the NOS activity, promoted NO production, further increased cGMP level and up-regulated PKG protein expression. These results suggested that gastrodin can promote hippocampal neurogenesis after cerebral ischemia and improve cognitive function in mice, which may be related to the activation of NO-cGMP-PKG signaling pathway. ©2019, Editorial Board of China Journal of Chinese Materia Medica. All right reserved. 

Cerebral ischemia; CGMP; Gastrodin; Hippocampus; Neurogenesis; NO; NOS; PKG