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Cardioprotective effects of transplanted adipose-derived stem cells under Ang II stress with Danggui administration augments cardiac function through upregulation of insulin-like growth factor 1 receptor in late-stage hypertension rats
Environmental Toxicology ( IF 4.5 ) Pub Date : 2021-04-21 , DOI: 10.1002/tox.23145
Parthasarathi Barik, Marthandam Asokan Shibu, Dennis Jine-Yuan Hsieh, Cecilia Hsuan Day, Ray-Jade Chen, Wei-Wen Kuo, Yung-Ming Chang, V. Vijaya Padma, Tsung-Jung Ho, Chih-Yang Huang

In aging hypertensive conditions, deterioration of insulin-like growth factor 1 receptor (IGF1R) cause a pathological impact on hypertensive hearts with an increased Ang II level. Recovering these adverse conditions through transplanted adipose-derived stem cells is a challenging approach. Moreover, Danggui, a Traditional Chinese medicine (TCM), is used for the treatment of cardioprotective effects. In this study, to evaluate whether the combined effect of MSCs and TCM can recover the cardiac function in late-stage hypertension rats. We observed that lower dose of Danggui crude extract treatment showed an increased level of cell viability with maintained stemness properties and growth rate in rat adipose-derived stem cells (rADSCs). Further, we cocultured the H9c2 cells with rADSCs and the results revealed that Danggui-treated MSCs enhanced the IGF1R expression and attenuated the hypertrophy in H9c2 cells against Ang II challenge by immunoblot and rhodamine-phalloidin staining. In addition, Danggui crude extract was also quantified and characterized by HPLC and LC–MS analysis. Furthermore, the in vivo study was performed by considering 11 months old rats (n = 7). Importantly, the oral administration of Danggui crude extract with stem cells intravenous injection in SHR-D-ADSCs group showed a combination effect to augment the cardiac function through enhancement of ejection fraction, fractional shortening, contractility function in the late-stage hypertension conditions. We have also observed a decreased apoptosis rate in the heart tissue of SHR-D-ADSCs group. Taken together, these results indicate that the combinatorial effects of Danggui crude extract and stem cell therapy enhanced cardiac function in late-stage SHR rats.

中文翻译:

当归给药在Ang II应激下移植脂肪干细胞的心脏保护作用通过上调胰岛素样生长因子1受体增强晚期高血压大鼠的心功能

在老化的高血压疾病中,胰岛素样生长因子 1 受体 (IGF1R) 的恶化会对高血压心脏造成病理影响,同时 Ang II 水平升高。通过移植的脂肪干细胞恢复这些不利条件是一种具有挑战性的方法。此外,当归是一种中药(TCM),用于治疗心脏保护作用。本研究旨在评价MSCs与中药联合作用能否恢复晚期高血压大鼠的心功能。我们观察到较低剂量的当归粗提取物处理显示出细胞活力水平增加,并保持大鼠脂肪来源干细胞 (rADSCs) 的干性特性和生长速度。此外,我们将 H9c2 细胞与 rADSCs 共培养,结果显示当归处理的 MSCs 通过免疫印迹和罗丹明-鬼笔环肽染色增强了 IGF1R 表达并减弱了 H9c2 细胞中针对 Ang II 攻击的肥大。此外,还通过 HPLC 和 LC-MS 分析对当归粗提物进行了定量和表征。此外,体内研究是通过考虑 11 个月大的大鼠 ( n = 7) 进行的。重要的是,当归口服SHR-D-ADSCs组干细胞粗提物静脉注射显示出联合作用,通过增强晚期高血压条件下的射血分数,缩短分数,收缩功能来增强心功能。我们还观察到 SHR-D-ADSCs 组心脏组织的细胞凋亡率降低。总之,这些结果表明当归粗提物和干细胞治疗的组合作用增强了晚期 SHR 大鼠的心脏功能。
更新日期:2021-06-03
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