Protective Effect of Astragaloside IV on High Glucose-Induced Endothelial Dysfunction via Inhibition of P2X7R Dependent P38 MAPK Signaling Pathway.
Protective Effect of Astragaloside IV on High Glucose-Induced Endothelial Dysfunction via Inhibition of P2X7R Dependent P38 MAPK Signaling Pathway.
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黄芪甲苷 IV 通过抑制 P2X7R 依赖性 P38 MAPK 信号通路对高糖诱导的内皮功能障碍的保护作用
DOI：
10.1155/2020/5070415
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发表时间：
2020
影响因子：
--
通讯作者：
Wang HX
中科院分区：
文献类型：
--
作者：
Leng B;Li C;Sun Y;Zhao K;Zhang L;Lu ML;Wang HX
血管内皮功能障碍与糖尿病患者死亡率增加相关。黄芪甲苷（Astragaloside IV，As-IV）是一种具有抗炎和抗内皮功能障碍作用的生物活性皂苷。然而，As-IV如何改善内皮功能障碍的潜在机制仍不清楚。因此，本研究旨在探讨As-IV对内皮功能障碍的保护作用及其分子生物学机制。在体内，大鼠腹腔注射链脲佐菌素（STZ），剂量为65 mg/kg体重，以建立糖尿病模型。在体外研究中，大鼠主动脉内皮细胞（RAOEC）预处理与AS-IV，SB 203580（p38 MAPK抑制剂）为2小时之前，添加高葡萄糖（33 mM葡萄糖）。我们的研究结果表明，作为-IV改善受损的内皮依赖性舒张和增加内皮一氧化氮合酶（eNOS）和一氧化氮（NO）的水平在体内和体外。此外，在体内和体外，As-IV治疗抑制糖尿病模型中升高的炎症和氧化应激。此外，在体内和体外，As-IV给药逆转了P2 X7 R和p-p38 MAPK的上调表达。此外，P2 X7 R siRNA和SB 203580对内皮细胞的作用与As-IV相似。总之，我们的研究表明，As-IV通过抑制P2 X7 R依赖的p38 MAPK信号通路来挽救高糖诱导的内皮功能障碍。这为进一步研究As-IV的血管内皮保护作用提供了理论依据。
Vascular endothelial dysfunction is associated with increased mortality in patients with diabetes. Astragaloside IV (As-IV) is a bioactive saponin with therapeutic potential as an anti-inflammatory and antiendothelial dysfunction. However, the underlying mechanism for how As-IV ameliorated endothelial dysfunction is still unclear. Therefore, in this study, we examined the protective effect of As-IV against endothelial dysfunction and explored potential molecular biology mechanism. In vivo, rats were intraperitoneally injected with streptozotocin (STZ) at a dose of 65 mg/kg body weight to establish a diabetic model. In vitro studies, rat aortic endothelial cells (RAOEC) were pretreated with As-IV, SB203580 (p38 MAPK inhibitor) for 2 h prior to the addition of high glucose (33 mM glucose). Our findings indicated that As-IV improved impaired endothelium-dependent relaxation and increased the levels of endothelial NO synthase (eNOS) and nitric oxide (NO) both in vivo and in vitro. Besides, As-IV treatment inhibited the elevated inflammation and oxidative stress in diabetic model both in vivo and in vitro. Moreover, As-IV administration reversed the upregulated expression of P2X7R and p-p38 MAPK in vivo and in vitro. Additionally, the effects of both P2X7R siRNA and SB203580 on endothelial cells were similar to As-IV. Collectively, our study demonstrated that As-IV rescued endothelial dysfunction induced by high glucose via inhibition of P2X7R dependent p38 MAPK signaling pathway. This provides a theoretical basis for the further study of the vascular endothelial protective effects of As-IV.
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影响因子：
2.7
作者：
Du, M;Wu, XJ;Branford-White, CJ
通讯作者：
Branford-White, CJ
DOI：
10.1042/cs20120479
发表时间：
2013-08
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Chiao CW;da Silva-Santos JE;Giachini FR;Tostes RC;Su MJ;Webb RC
通讯作者：
Webb RC
影响因子：
3
作者：
Fisk, Marie;Gajendragadkar, Parag R.;Cheriyan, Joseph
通讯作者：
Cheriyan, Joseph
影响因子：
37.8
作者：
Förstermann, U;Münzel, T
通讯作者：
Münzel, T
影响因子：
--
作者：
He Y;Xi J;Zheng H;Zhang Y;Jin Y;Xu Z
通讯作者：
Xu Z