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Study on the impact of catalpol on brain tissue damage in rats with subarachnoid hemorrhage based on Raf-MEK-ERK signal pathway
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DOI   10.11656/j.issn.1672-1519.2023.08.19
Key Words   catalpol;subarachnoid hemorrhage;brain tissue damage;Raf-MEK-ERK signal pathway
Author NameAffiliationE-mail
MENG Yanju Department of Neurosurgery, Puyang People's Hospital, Puyang 457005, China  
WANG Lu Department of Anesthesiology, Puyang People's Hospital, Puyang 457005, China  
WANG Xianqing Department of Neurosurgery, Puyang People's Hospital, Puyang 457005, China  
HAO Zhiyong Department of Neurosurgery, Puyang People's Hospital, Puyang 457005, China puyangpuyang2021@163.com 
Abstract
    [Objective] To investigate the effect of catalpol on serine/threonine kinase(Raf)-mitogen activated protein kinase(MEK)-extracellular regulated protein kinase(ERK) signaling pathway in brain tissue of rats with subarachnoid hemorrhage(SAH),and to explore the mechanism of catalpol against SAH brain injury. [Methods] Rats were randomly grouped into sham operation group,SAH group,catalpol group,and catalpol+U0126 group(catalpol+Raf-MEK-ERK signal pathway inhibitor U0126). A rat SAH model was established using intravascular perforations. And evaluate neural function and SAH grading in rats. Evans Blue(EB) was applied to detect blood brain barrier permeability. Hematoxylin eosin(HE) staining was applied to observe pathological changes in brain tissue. Immunofluorescence staining was applied to detect neuronal apoptosis and the expression of LC3-Ⅱ,p-ERK positive cells. Western blot was used to detect the expression of Raf,MEK,phosphorylation(p)-MEK,ERK1/2,p-ERK1/2,B-cell lymphoma 2 (Bcl-2),Bcl-2 related X protein(Bax),autophagy gene Beclin-1,and microtubule associated proteinlight chain 3-Ⅱ(LC3-Ⅱ) in brain tissue. [Results] Compared with the sham operation group,the neuronal cells in the SAH group were loosely arranged and the number decreased,the SAH grading,brain tissue water content,EB exudation,TUNEL positive cells,apoptosis rate,LC3-Ⅱ,p-ERK positive expression,Bax,Beclin-1,LC3-Ⅱ,Raf,p-MEK/MEK,p-ERK1/2/ERK1/2 expression increased obviously,the neurological function score and Bcl-2 expression decreased (P<0.05);compared with the SAH group,the neuronal damage in the catalpol group reduced obviously,and cell death reduced,SAH grade,brain tissue water content,EB exudation,TUNEL positive cell count,apoptosis rate,Bax decreased obviously,and neurological function score,Bcl-2 expression increased,LC3-Ⅱ,p-ERK positive expression,Bax,Beclin-1,LC3-Ⅱ,Raf,p-MEK/MEK,p-ERK1/2/ERK1/2 expression further increased (P<0.05);Raf-MEK-ERK pathway inhibitor U0126 was able to reverse the improvement effect of catalpol on brain tissue damage (P<0.05). [Conclusion] Catalpol may promote autophagy of neural cells and improve brain injury in SAH rats by activating the Raf-MEK-ERK signaling pathway.

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