Soy isoflavones alleviates calcium overload in rats with cerebral ischemia-reperfusion by inhibiting the Wnt/Ca2+signaling pathway
10.12122/j.issn.1673-4254.2024.06.05
- VernacularTitle:大豆异黄酮通过抑制Wnt/Ca2+信号通路减轻大鼠脑缺血再灌注引起的钙超载
- Author:
Li LI
1
,
2
;
Mengzhe WANG
;
Saisai LIU
;
Xiaonan ZHANG
;
Jie CHEN
;
Weiting TAO
;
Shai LI
;
Zhiwen QING
;
Quanfang TAO
;
Yi LIU
;
Li HUANG
;
Shidi ZHAO
Author Information
1. 蚌埠医科大学 病理生理学教研室,安徽 蚌埠 233000
2. 蚌埠医科大学 心脑血管疾病基础与临床重点实验室,安徽 蚌埠 233000
- Keywords:
soy isoflavones;
cerebral ischemia-reperfusion;
calcium overload;
Wnt/Ca2+signaling pathway
- From:
Journal of Southern Medical University
2024;44(6):1048-1058
- CountryChina
- Language:Chinese
-
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/Ca2+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,Ca2+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(P<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/Ca2+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/Ca2+signaling pathway.
