[Soy Isoflavones Alleviates Calcium Overload in Rats with Cerebral Ischemia-reperfusion by Inhibiting the Wnt/Ca Signaling Pathway]

Overview

Journal Nan Fang Yi Ke Da Xue Xue Bao

Specialty General Medicine

Date 2024 Jul 8

PMID 38977334

Authors

L Li

M Wang

S Liu

X Zhang

J Chen

W Tao

S Li

Z Qing

Q Tao

Y Liu

L Huang

S Zhao

Affiliations

Soon will be listed here.

Abstract

Objective: To explore the mechanism by which soybean isoflavone (SI) reduces calcium overload induced by cerebral ischemia-reperfusion (I/R).

Methods: Forty-eight SD rats were randomized into 4 groups to receive sham operation, cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion (I/R model group), or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca signaling pathway.Calcium levels and pathological changes in the ischemic penumbra (IP) were measured using calcium chromogenic assay and HE staining, respectively.Another 72 SD randomly allocated for sham operation, I/R modeling, or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter, and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining, and ROS level, Ca level, cell apoptosis, and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry; the protein expressions of Wnt5a, Frizzled-2, and P-CaMK Ⅱ in the IP were detected with Western blotting and immunohistochemistry.

Results: In rats with cerebral I/R, Frizzled-2 knockdown significantly lowered calcium concentration ( < 0.001) and the expression levels of Wnt5a, Frizzled-2, and P-CaMK Ⅱ in the IP area.In soy isoflavones-pretreated rats, calcium concentration, ROS and MDA levels, cell apoptosis rate, cerebral infarct volume, and expression levels of Wnt/Ca signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.

Conclusion: Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca signaling pathway.

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