Effect of Yiyin Tongluo Formula on Ischemic Stroke Rats Based on the PI3K-AKT-mTOR Signaling Pathway
Objective To observe the protective effect and mechanisms of Yiyin Tongluo Formula on cerebral tis-sue in a rat model of cerebral ischemic stroke(CIS).Methods Seventy-two 2-month-old SPF-grade Wistar rats were randomly divided into a sham group(n=10)and an experimental group(n=62).The CIS rat model was established using the Longa suture method.The experimental rats were further divided into a model group,low-,medium-,and high-dose Yiyin Tongluo Formula groups,and a nimodipine group,with 9 rats in each group.The intervention lasted for 7 days.The cerebral infarct volume was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC)staining method.Lev-els of superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)in brain tissue were measured using enzyme-linked immunosorbent assay(ELISA).Autophagic ultrastructure in brain tissue was observed u-sing transmission electron microscopy.The mRNA expression levels of Beclin-1,microtubule-associated protein 1 light chain 3(LC-3),phosphatidylinositol-3-kinase(PI3K),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)in brain tissue were detected using real-time polymerase chain reaction(RT-PCR).Protein expression levels of Beclin-1,LC-3,PI3K,AKT,and mTOR were analyzed using Western blotting.Results Compared with the sham group,the model group showed a significantly increased cerebral infarct area(P＜0.01),marked ultrastructural changes,significantly decreased SOD and GSH-Px levels(P＜0.01),significantly increased MDA levels(P＜0.05),significantly elevated expression levels of Beclin-1 and LC-3 genes and proteins(P＜0.01),and significantly reduced expression levels of PI3K,AKT,and mTOR(P＜0.01).Compared with the model group,the nimodipine group and the high-dose Yiyin Tongluo Formula group showed significantly reduced cerebral infarct areas(P＜0.01),more regular pathological morphology,and better-preserved ultrastructure.These groups also demonstrated significantly increased SOD and GSH-Px levels(P＜0.05),significantly decreased MDA levels(P＜0.05),reduced Beclin-1 and LC-3 gene and protein ex-pression levels(P＜0.05,P＜0.01),and significantly increased expression levels of PI3K,AKT,and mTOR(P＜0.05,P＜0.01).Conclusion Yiyin Tongluo Formula has a protective effect on brain injury in a rat model of CIS.Its mechanism may involve the regulation of key protein expression in the PI3 K/AKT/mTOR signaling pathway,improvement of SOD,MDA,and GSH-Px secretion,and inhibition of neuronal autophagy activity.
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维普
