Effects of Soybean Isoflavone on the Notch Signal Pathway of the Brain in Rats with Cerebral Ischemia

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The aim of this study was to test the hypothesis that gastric lavage with soybean isoflavone activates the Notch signaling pathway and prevents apoptosis in the cerebral cortex during experimental strokes. Sprague-Dawley rats were randomly assigned to four groups of 10 rats each: sham operation plus vehicle (Sham), middle cerebral artery occlusion plus vehicle (MCAO), MCAO plus low dose soybean isoflavone (10 mg/(kg·d)) and MCAO plus high dose soybean isoflavone (50 mg/(kg·d)). The vehicle (saline, 10 mL/(kg·d)) and soybean isoflavone were administered by gastric lavage for 28 d prior to sham or MCAO operation and for 7 d afterward. The mRNA and protein expression levels of components of the Notch signaling system (Notch1 and Hes5) were measured by in situ hybridization and western blotting, respectively, whereas apoptosis was quantified by TUNEL assay. The results showed that MCAO stimulated expression of Notch1 and Hes5, at both the mRNA and protein levels, and also increased apoptosis. Soybean isoflavone dose-dependently augmented the stimulatory effect of MCAO on Notch1 and Hes5 expression levels but decreased apoptosis. These results identify a possible mechanism by which soybean isoflavone confers neuroprotection in strokes.
2009-08-01