[Soy isoflavones alleviates calcium overload in rats with cerebral ischemia-reperfusion by inhibiting the Wnt/Ca²⁺ signaling pathway].

Q3 Medicine Nan fang yi ke da xue xue bao = Journal of Southern Medical University Pub Date : 2024-06-20 DOI:10.12122/j.issn.1673-4254.2024.06.05

L Li, M Wang, S Liu, X Zhang, J Chen, W Tao, S Li, Z Qing, Q Tao, Y Liu, L Huang, S Zhao

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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.

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[大豆异黄酮通过抑制 Wnt/Ca2+ 信号通路减轻脑缺血再灌注大鼠的钙超载】。］

摘要探讨大豆异黄酮（SI）减轻脑缺血再灌注（I/R）引起的钙超载的机制：方法：将48只SD大鼠随机分为4组，分别接受假手术、大脑中动脉闭塞2小时后再灌注24小时（I/R模型组）或在大脑侧脑室注射携带Frizzled-2 siRNA的腺相关病毒或空病毒载体（I/R模型组）。缺血半影（IP）的钙水平和病理变化分别用钙染色法和HE染色法测量。用多普勒血流仪检查了区域脑血流量，并用TTC染色法评估了脑梗死体积。用HE和Nissl染色法评估IP区域的病理变化，用免疫荧光法或流式细胞术分析ROS水平、Ca2+水平、细胞凋亡和细胞内钙浓度；用Western印迹法和免疫组化法检测IP中Wnt5a、Frizzled-2和P-CaMK Ⅱ的蛋白表达：结果：在脑I/R大鼠中，Frizzled-2基因敲除可显著降低钙离子浓度（P < 0.001）以及IP区Wnt5a、Frizzled-2和P-CaMK Ⅱ的表达水平。大豆异黄酮预处理组大鼠的钙浓度、ROS和MDA水平、细胞凋亡率、脑梗死体积和Wnt/Ca2+信号通路相关蛋白的表达水平均明显低于I/R模型组大鼠，而SOD水平高于I/R模型组大鼠：结论：大豆异黄酮能通过抑制Wnt/Ca2+信号通路减轻脑I/R大鼠的钙超载。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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