Ginsenoside Rg1 attenuates mechanical stress-induced cardiac injury via calcium sensing receptor-related pathway.
Ginsenoside Rg1 attenuates mechanical stress-induced cardiac injury via calcium sensing receptor-related pathway.
复制标题
DOI：
10.1016/j.jgr.2021.03.006
复制
发表时间：
2021-11
影响因子：
6.3
通讯作者：
Wang HX
中科院分区：
文献类型：
--
作者：
Lu ML;Wang J;Sun Y;Li C;Sun TR;Hou XW;Wang HX
人参皂苷Rg 1（Ginsenoside Rg 1，Rg 1）具有良好的抗心血管疾病作用。本研究从钙敏感受体（CaSR）信号通路入手，探讨人参皂甙Rg 1对机械应激性心肌损伤的影响及其可能机制。通过腹主动脉缩窄（AAC）程序对大鼠施加机械应力，并通过Bioflex胶原蛋白I板的机械拉伸对心肌细胞和心脏成纤维细胞施加机械应力。在大鼠和细胞水平观察Rg 1对心肌细胞肥大、纤维化、心功能、[Ca 2 +]i、CaSR和钙调神经磷酸酶（CaN）表达的影响。Rg 1可减轻AAC诱导的大鼠心肌组织、培养的心肌细胞和心肌成纤维细胞的肥大和纤维化，改善心脏失代偿。更重要的是，Rg 1处理抑制CaSR表达和[Ca 2 +]i增加，这与CaSR抑制剂NPS 2143相似。此外，Rg 1处理抑制CaN和TGF-β1通路的激活。机制分析表明，CaSR激动剂GdCl 3不能进一步增加机械牵张诱导的心肌细胞[Ca 2 +]i和CaN通路相关蛋白的表达。CaN抑制剂CsA可抑制心肌肥厚、心肌纤维化、[Ca ~（2+）]i和CaN信号转导，但对CaSR表达无影响。CaN通路的激活和CaSR介导的[Ca 2 +]i升高参与了心肌肥厚和纤维化的发生，这可能是Rg 1抗心肌损伤的作用靶点。人参皂苷Rg 1通过下调CaSR保护心肌的机制AAC通过CaSR/IP 3R途径诱导[Ca 2 +]i超载。[Ca 2 +]i升高导致CaN信号通路激活，导致心肌肥厚和纤维化。人参皂苷Rg 1通过抑制[Ca 2 +]i，下调CaSR、CaN和TGF-β1信号通路，抑制心肌肥厚和纤维化。
Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca2+]i, and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca2+]i, which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-β1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl3 could not further increase the [Ca2+]i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca2+]i and CaN signaling but had no effect on CaSR expression. The activation of CaN pathway and the increase of [Ca2+]i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury. The mechanism of cardioprotection by Ginsenoside Rg1 via downregulation of CaSR. AAC induces overload of [Ca2+]i through CaSR/IP3R pathway. The increased [Ca2+]i leads to activation of CaN signaling pathway, resulting in cardiac hypertrophy and fibrosis. Ginsenoside Rg1 inhibits cardiac hypertrophy and fibrosis through inhibiting [Ca2+]i and downregulation of CaSR, CaN and TGF-β1 signaling pathways.
登录
查看更多内容
影响因子：
4
作者：
Li L;Pan CS;Yan L;Cui YC;Liu YY;Mu HN;He K;Hu BH;Chang X;Sun K;Fan JY;Huang L;Han JY
通讯作者：
Han JY
DOI：
10.1016/j.bbrc.2018.02.098
发表时间：
2018-03-04
影响因子：
3.1
作者：
Chi, Jinyu;Wang, Lei;Yin, Xinhua
通讯作者：
Yin, Xinhua
钙敏感受体通过线粒体动力学在自发性高血压大鼠代偿性肥大心肌细胞凋亡中的作用
DOI：
10.1016/j.bbrc.2017.04.126
发表时间：
2017-06-03
影响因子：
3.1
作者：
Hong, Siting;Zhang, Xin;Yin, Xinhua
通讯作者：
Yin, Xinhua
去肾神经通过心脏和大脑氧化应激的双重调节改善大鼠梗死后心脏重塑
影响因子：
7.5
作者：
Jiang, Wan-Ying;Huo, Jun-Yu;Shan, Qi-Jun
通讯作者：
Shan, Qi-Jun
影响因子：
3.9
作者：
Jiang, Chun-ming;Han, Li-Ping;Li, Wei-ming
通讯作者：
Li, Wei-ming