Mechanism of Yixuanning Granules on Ischemic Vertigo Based on SIRT1/PGC-1α Signaling Pathway
WANG Furong
LI Mingkun
LIU Zhiguang
MA Jinbo
Abstract：Objective:To investigate the regulatory effect of Yixuanning granules on silencing information regulatory factor 1(SIRT1)/peroxisome proliferator-activated receptor γ-coactivator 1α(PGC-1α)signaling pathway and its improvement effect on vertigo symptoms of ischemic vertigo in rats.Methods:After 3 days of escape reflex training of electrical stimulation,rat model of ischemic vertigo was established,and the rats were divided into model group,Yixuanning granules group(6 g/kg),SIRT1 inhibitor(EX527)group(5 mg/kg),Yixuanning granules+EX527 group(Yixuanning granules 6 g/kg+EX527 5 mg/kg).Each group was given drug for 7 days.Another 16 rats were selected as sham group(pre-modeling training,only threading without ligature).The stage escape latency of rats was measured by the stage escape experiment.The blood flow in vestibular nucleus of rats was measured by Doppler laser blood flow analyzer,and the decreasing rate of blood flow was calculated.Hematoxylin-eosin staining was used to observe the pathological characteristics of rat brain.The activities of malondialdehyde(MDA),superoxide dismutase(SOD),nitric oxide(NO),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of SIRT1,PGC-1α,B-lymphoblastoma-2-associated X protein(Bax)and B-lymphoblastoma-2(Bcl-2)in rat brain were detected by Western Blot.Results:Compared with sham group,brain nerve cells in the model group were deformable,constricted and apoptotic,stage escape latency blood flow rate decreased after administration,the activity of MDA,NO,IL-1β,TNF-α content and Bax protein expressions in cerebral tissue increased(P<0.05).SOD activity,SIRT1,PGC-1α and Bcl-2 protein expressions decreased(P<0.05).Compared with model group,the number of apoptotic cells in brain tissue of Yixuanning granules group decreased,the number of normal cells around glia increased significantly,the latency of stage escape,the decrease rate of blood flow after administration,the activity of MDA,NO,IL-1β,TNF-αcontent and Bax protein expressions in cerebral tissue decreased(P<0.05).SOD activity,SIRT1,PGC-1αand Bcl-2 protein expressions increased(P<0.05).Cerebral nerve cells in the EX527 group deformated severely,with obvious signs of contraction and apoptosis,and the activity of MDA,NO,IL-1β,TNF-α content and Bax protein expressions in brain tissue increased(P<0.05),SOD activity,SIRT1,PGC-1αand Bcl-2 protein expressions decreased(P<0.05).EX527 could reverse the improvement effect of Yixuanning granules on ischemic vertigo in rats(P<0.05).Conclusion:Yixuanning granules might improve vertigo symptoms of ischemic vertigo in rats by activating the SIRT1/PGC-1α pathway and inhibiting oxidative stress and inflammatory responses.
Keywords：ischemic vertigoYixuanning granulessilencing information regulatory factor 1/peroxisome proliferator-activated receptor γ-coactivator 1αSIRT1/PGC-1αratsexperimental study
Publication Date：2024-05-16
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1787-1792 )