The protective effect of allicin on myocardial ischemia-reperfusion by inhibition of Ca(2+) overload-induced cardiomyocyte apoptosis via the PI3K/GRK2/PLC-γ/IP3R signaling pathway.
The protective effect of allicin on myocardial ischemia-reperfusion by inhibition of Ca(2+) overload-induced cardiomyocyte apoptosis via the PI3K/GRK2/PLC-γ/IP3R signaling pathway.
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大蒜素通过PI3K/GRK2/PLC-γ/IP3R信号通路抑制Ca2超载诱导的心肌细胞凋亡对心肌缺血再灌注的保护作用
DOI：
10.18632/aging.203375
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发表时间：
2021-08-03
期刊：
影响因子：
--
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Gao T;Yang P;Fu D;Liu M;Deng X;Shao M;Liao J;Jiang H;Li X
目的：探讨大蒜素对心肌缺血再灌注（MI/R）损伤的保护作用及其机制。研究方法：我们从磷脂酰肌醇3-激酶、G蛋白偶联受体激酶2、磷脂酶Cγ和心肌细胞凋亡等方面探讨大蒜素减轻MI/R损伤的机制。将60只雄性小鼠随机分为3组：重复MI/R组（模型组）、假手术组（对照组）和MI/R+大蒜素组（大蒜素组）。超声检查心脏功能。Masson染色观察心肌梗死面积。采用TUNEL法检测大蒜素的抗凋亡作用。通过mRNA微阵列分析差异表达基因（DEG）和通路。采用免疫荧光染色和western blot检测大蒜素对PI 3 K的影响。应用泛PLC激活剂m-3 M3 FBS研究大蒜素是否通过GRK 2/PLC/IP 3R信号通路诱导心肌细胞凋亡。结果如下：Masson染色和TUNEL法显示，大蒜素减少心肌梗死面积，并在M/IR中发挥抗凋亡作用。超声检查显示，大蒜素改善M/IR损伤后的心功能。基因本体分析表明，钙信号通路和PI 3 KCA（PI 3 K）被选中。免疫荧光染色和western blot显示大蒜素在MI/R损伤过程中激活PI 3 K。Fura-2AM染色结果提示，大蒜素可能通过PI 3 K介导的GRK 2/PLC-γ/IP 3R信号通路对MI/R损伤起到保护作用。结论：大蒜素对心肌缺血再灌注损伤具有保护作用。其作用机制可能与抑制Ca 2+过负荷诱导的细胞凋亡和抑制PI 3 K介导的GRK 2/PLC-γ/IP 3R信号通路有关。
Purpose: To investigate the protective effect and mechanism of allicin on myocardial ischemia-reperfusion (MI/R) injury. Methods: We investigated the mechanisms by which allicin attenuated the MI/R injury by focusing on phosphoinositide 3-kinase, G protein coupled receptor kinases 2, phospholipase Cγ and cardiomyocyte apoptosis. Sixty male mice were randomly assigned into three groups: repeated MI/R (model), sham-operated (control), and MI/R+ allicin group (allicin). Ultrasound examination was used to examine the cardiac function. Masson staining was used to evaluate the myocardial infarct area. TUNEL assay was performed to examine the anti-apoptotic effect of allicin. Differentially expressed genes (DEGs) and pathways were analyzed by mRNA microarray analysis. Immunofluorescence staining and western blot were carried out to detect the effect of allicin on the PI3K. A pan-PLC activator, m-3M3FBS, was applied to investigate whether allicin induced cardiomyocyte apoptosis was via the GRK2/PLC/IP3R signaling pathway. Results: Masson staining and the TUNEL assay revealed that allicin reduced infarct size and played an anti-apoptotic role in M/IR. Ultrasound examination revealed that allicin improved cardiac function after M/IR injury. Gene ontology analysis indicated that the calcium signaling pathway and PI3KCA(PI3K) were selected. Immunofluorescence staining and western blot exposed that PI3K was activated by allicin during MI/R injury. Fura-2AM staining revealed that the PI3K -mediated GRK2/PLC-γ/IP3R pathway may be involved in the protective effect of allicin on MI/R injury. Conclusions: Allicin has a protective effect on MI/R injury. This effect might be associated with the inhibition of Ca2+ overload-induced apoptosis and the inhibition of the PI3K -mediated GRK2/PLC-γ/IP3R signaling pathway.
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DOI：
10.1016/j.bbrc.2017.02.136
发表时间：
2017-04-15
影响因子：
3.1
作者：
Kim, Jihwa;Kim, Jooyeon;Park, Woo Jin
通讯作者：
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影响因子：
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作者：
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影响因子：
2.6
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DOI：
10.1152/ajpgi.00440.2013
发表时间：
2014-05-01
影响因子：
4.5
作者：
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影响因子：
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