BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK signaling pathways contribute to neurorestorative effect of Houshiheisan against cerebral ischemia injury in rats

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• 作者：Jiahui Chang^a ; ^b ; ¹ ; Xiaoquan Yao^a ; ^b ; ¹ ; Haiyan Zou^a ; ^b ; Lei Wang^a ; ^b ; Yue Lu^a ; ^b ; Qiuxia Zhang^a ; ^b ; ^{zqx1310@sina.com} ; Hui Zhao^a ; ^b ; ^{zhaohuishouyi@sina.com}
• 关键词：t-PA ; Tissue-type plasminogen activator ; CNS ; central nervous system ; Nogo-A ; neurite outgrowth inhibition protein A ; TCM ; Traditional Chinese medicine ; HSHS ; Houshiheisan ; NGF ; nerve growth factor ; APP ; amyloid precursor protein ; BDNF ; Brain-derived neurotrophic factor ; NgR ; Nogo receptor ; HPLC ; high performance liquid chromatography ; pMCAO ; permanent middle cerebral artery occlusion ; CCA ; common carotid artery ; ECA ; external carotid artery ; ICA ; internal carotid artery ; HE ; hematoxylin and eos
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：24 December 2016
• 年：2016
• 卷：194
• 期：Complete
• 页码：1032-1042
• 全文大小：1608 K
• 卷排序：194

文摘

Houshiheisan (HSHS), a classic traditional medicine prescription, has notable effects on patients with strokeAim of the studyTo investigate the neurorestorative effects of HSHS on ischemic stroke and explore its mode of action.Materials and methodsFocal cerebral ischemia models were induced by permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley (SD) rats were randomly divided into 5 experimental groups: sham vehicle, ischemia vehicle, pMCAO+HSHS at 5.1, 10.2 g/kg, and pMCAO+Ginaton 0.028 g/kg. HSHS or Ginaton was administrated 6 h after pMCAO onset. Neurological function was assessed and then rats were sacrificed 7 days after MCAO. Cerebral ischemic injury was evaluated by hematoxylin and eosin (HE) staining and Neuronal nuclear antigen (NeuN) immunofluorescence analysis. The levels of BDNF were detected by enzyme linked immunosorbent assay (ELISA), and the expression levels of PI3K/Akt and Nogo-A/RhoA/ROCK2 signaling pathway were detected by western blot and quantitative real-time PCR (qRT-PCR).ResultsCompared with those results of pMCAO group, HSHS 5.1 and HSHS 10.2 groups markedly improved neurological function, alleviated pathological damage, promoted the neuronal survival, increased the expression of BDNF, PI3K, Akt, in protein and mRNA, decreased the expression of Nogo-A, NgR, RhoA and ROCK2 in protein and mRNA 7 days after pMCAO.ConclusionsThe findings demonstrate that HSHS had significant therapeutic effects on ischemic stroke and it perhaps worked through the activation of BDNF/PI3K/Akt and down-regulation of Nogo-A/RhoA/ROCK signaling pathways.