Department of Ultrasound, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.
Department of Ultrasound, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province, China.
Bioengineered. 2022 Apr;13(4):8419-8431. doi: 10.1080/21655979.2022.2050481.
The aim of this study was to investigate the cardioprotective effects and probable mechanism of ultrasound-targeted microbubble destruction (UTMD) combined with astragalus polysaccharide (APS) on diabetic cardiomyopathy (DCM) model rats. The DCM rats with diabetes and cardiomyopathy were induced via chronic treatment of doxorubicin and then randomly divided into the (1) DCM model group; (2) APS microbubble group; (3) UTMDgroup; and (4) APS microbubbles combined with UTMD group. After 4-week intervention, the fasting blood glucose levels, body weight, %HbA1c level and glucose tolerance of DCM rats received combination therapy were significantly improved as compared with those of UTMD or saline-treated ones. Moreover, the heart/body weight ratio, and myocardial contractility were all improved after receiving combination therapy groups compared with others. In addition, significantly upregulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as significantly downregulated malondialdehyde (MDA) levels were all observed in the ones received combined treatment compared to others. Furthermore, the lipid accumulation and the expression levels of inflammatory factors were all significantly down-regulated in those ones received combination therapy compared with others (all < 0.05). Further pathological analysis demonstrated that combination therapy effectively ameliorated fibrosis and myocardial morphological changes of DCM rats via activating the upregulation of AMPK and PPAR-γ signaling pathway, and inhibiting NF-κB activity in myocardial tissues of DCM rats. In conclusion, APS microbubbles combined with UTMD effectively protect the myocardial injury of DCM rats via activating AMPK signaling pathway to alleviate inflammation response, fibrosis and oxidative stress in myocardial tissues.
本研究旨在探讨超声靶向微泡破坏（UTMD）联合黄芪多糖（APS）对糖尿病心肌病（DCM）模型大鼠的心脏保护作用及其可能机制。通过慢性阿霉素处理诱导糖尿病伴心肌病大鼠建立 DCM 模型，然后将其随机分为（1）DCM 模型组；（2）APS 微泡组；（3）UTMD 组；和（4）APS 微泡联合 UTMD 组。经过 4 周的干预，联合治疗组的 DCM 大鼠的空腹血糖水平、体重、%HbA1c 水平和葡萄糖耐量均明显优于 UTMD 组或生理盐水组。此外，联合治疗组的心脏/体重比和心肌收缩力均优于其他组。此外，与其他组相比，联合治疗组的超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性显著升高，丙二醛（MDA）水平显著降低。此外，与其他组相比，联合治疗组的脂质堆积和炎症因子的表达水平均显著降低（均 < 0.05）。进一步的病理分析表明，联合治疗通过激活 AMPK 和 PPAR-γ 信号通路的上调，抑制 DCM 大鼠心肌组织中 NF-κB 的活性，有效改善了 DCM 大鼠的纤维化和心肌形态变化。总之，APS 微泡联合 UTMD 通过激活 AMPK 信号通路有效保护 DCM 大鼠的心肌损伤，减轻心肌组织中的炎症反应、纤维化和氧化应激。
