Polydatin Protects Diabetic Heart against Ischemia-Reperfusion Injury via Notch1/Hes1-Mediated Activation of Pten/Akt Signaling.
Polydatin Protects Diabetic Heart against Ischemia-Reperfusion Injury via Notch1/Hes1-Mediated Activation of Pten/Akt Signaling.
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虎杖甙通过 Notch1/Hes1 介导的 Pten/Akt 信号激活保护糖尿病心脏免受缺血再灌注损伤
DOI：
10.1155/2018/2750695
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发表时间：
2018
影响因子：
--
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Yu L;Li Z;Dong X;Xue X;Liu Y;Xu S;Zhang J;Han J;Yang Y;Wang H
糖尿病加重心肌缺血再灌注（MI/R）损伤时的氧化/硝化应激。最近的研究强调了多柚素的心脏保护作用。然而，其对糖尿病性MI/R损伤的影响及其潜在机制尚不清楚。本研究以Notch1/Hes1信号通路和心肌氧化/硝化应激为研究重点，探讨了多丹素对糖尿病心肌梗死/再灌注损伤的影响。在不含或不含DAPT（一种γ-分泌酶抑制剂）或LY294002（一种PI3K/Akt抑制剂）的情况下，给予链脲佐菌素（STZ-）诱导的糖尿病大鼠20 mg/kg/d，然后进行MI/R损伤。给药保心功能，减少心肌梗死面积。此外，通过降低心肌超氧化物生成、丙二醛、gp91phox表达、iNOS表达、NO代谢物水平和硝基酪氨酸含量以及增加eNOS磷酸化，多柚素改善了心肌氧化/硝化应激损伤。然而，这些作用被DAPT阻断。DAPT还能抑制多聚丹素对糖尿病心肌Notch1/Hes1-Pten/Akt信号通路的刺激作用。此外，LY294002不仅可以消除多葡苷的抗凋亡作用，还可以逆转其对心肌氧化/硝化应激的抑制作用。多聚胆碱通过改善氧化/硝酸盐应激损伤，有效减轻糖尿病患者心肌梗死/心肌梗死损伤，改善左心室功能恢复。重要的是，Notch1/ hes1介导的Pten/Akt信号激活在这一过程中发挥了至关重要的作用。
Diabetes exacerbates oxidative/nitrative stress during myocardial ischemia-reperfusion (MI/R) injury. Recent studies highlighted the cardioprotective actions of polydatin. However, its effect on diabetic MI/R injury and the underlying mechanisms remain unknown. This work was undertaken to evaluate the effect of polydatin on diabetic MI/R injury with a focus on Notch1/Hes1 signaling and myocardial oxidative/nitrative stress. Streptozotocin- (STZ-) induced diabetic rats were administered with polydatin (20 mg/kg/d) in the absence or presence of DAPT (a γ-secretase inhibitor) or LY294002 (a PI3K/Akt inhibitor) and then subjected to MI/R injury. Polydatin administration preserved cardiac function and reduced myocardial infarct size. Moreover, polydatin ameliorated myocardial oxidative/nitrative stress damage as evidenced by decreased myocardial superoxide generation, malondialdehyde, gp91phox expression, iNOS expression, NO metabolite level, and nitrotyrosine content and increased eNOS phosphorylation. However, these effects were blocked by DAPT administration. DAPT also inhibited the stimulatory effect of polydatin on the Notch1/Hes1-Pten/Akt signaling pathway in a diabetic myocardium. Additionally, LY294002 not only abolished polydatin's antiapoptotic effect but also reversed its inhibitory effect on myocardial oxidative/nitrative stress. Polydatin effectively reduced MI/R injury and improved left ventricular functional recovery under diabetic condition by ameliorating oxidative/nitrative stress damage. Importantly, Notch1/Hes1-mediated activation of Pten/Akt signaling played a crucial role in this process.
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影响因子：
16.6
作者：
Kerr BA;West XZ;Kim YW;Zhao Y;Tischenko M;Cull RM;Phares TW;Peng XD;Bernier-Latmani J;Petrova TV;Adams RH;Hay N;Naga Prasad SV;Byzova TV
通讯作者：
Byzova TV
虎杖甙后处理可通过促进自噬通量减轻心肌缺血/再灌注损伤。
影响因子：
6
作者：
Ling, Yuanna;Chen, Guiming;Chen, Aihua
通讯作者：
Chen, Aihua
影响因子：
4.6
作者：
Isfort, Michael;Stevens, Sarah C. W.;Schaffer, Stephen;Jong, Chian Ju;Wold, Loren E.
通讯作者：
Wold, Loren E.
影响因子：
9.3
作者：
Baranyai T;Nagy CT;Koncsos G;Onódi Z;Károlyi-Szabó M;Makkos A;Varga ZV;Ferdinandy P;Giricz Z
通讯作者：
Giricz Z
NOTCH1 在透明细胞肾细胞癌中通过调节 PTEN/PI3K/AKT 通路发挥癌基因的作用。
DOI：
10.1016/j.urolonc.2011.07.006
发表时间：
2013-08-01
影响因子：
2.7
作者：
Liu, Shangwen;Ma, Xin;Zhang, Xu
通讯作者：
Zhang, Xu