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载葛根素超声微泡对比剂用于糖尿病心肌病大鼠的声动力学治疗。

Puerarin-loaded ultrasound microbubble contrast agent used as sonodynamic therapy for diabetic cardiomyopathy rats.

机构信息

School of Pharmacy, Xinxiang Medical University, Xinxiang, 453002, Henan Province, PR China.

Department of Ultrasonography, Fuwai Hospital of Central China, Henan Provincial Peoples Hospital (People's Hospital of Zhengzhou University), Zhengzhou, Henan, 450003, PR China.

出版信息

Colloids Surf B Biointerfaces. 2020 Jun;190:110887. doi: 10.1016/j.colsurfb.2020.110887. Epub 2020 Feb 20.

Abstract

In this study, a puerarin-loaded ultrasound sulfur hexafluoride microbubble contrast agent as a sonodynamic therapy (SDT) was developed to improve targeted drug delivery and pharmacodynamic effects in diabetic cardiomyopathy (DCM) treatment. Fluorescence microscope morphology was applied to confirm the fabrication of the puerarin - microbubbles (PMBs). The average size distribution and zeta potential of PMBs were 760.0 ± 101.2 nm and -20.4 ± 6.59 mV, respectively. In vitro and in vivo experiments were carried out to study the pharmacodynamic effects and targeted drug delivery of PMBs. The cytotoxicity, assessed by the cell viability of human umbilical vein endothelial cells (HUVECs), showed that the microbubbles were nontoxic even in high concentration of 2.500 mg/mL, and the wound healing scratch assay proved that PMBs cloud obviously improve the migration ability of HUVECs. Furthermore, streptozotocin (STZ) accompanied with high-energy diets was employed to build the DCM rat model. The blood glucose, histological changes of the pancreas and heart, and cardiac function were used to confirm the obtainment of the DCM rat model. Histological and physiological changes of the PMBs treatment group indicated that PMBs had a significant therapeutic efficacy when compared to the DCM model group. Therefore, PMBs are a promising strategy for a targeted drug delivery system and a novel noninvasive treatment for DCM.

摘要

在这项研究中,研制了一种葛根素负载的超声六氟化硫微泡造影剂作为声动力学疗法(SDT),以提高糖尿病心肌病(DCM)治疗中的靶向药物输送和药效。荧光显微镜形态学用于确证葛根素-微泡(PMBs)的制备。PMBs 的平均粒径分布和 zeta 电位分别为 760.0±101.2nm 和-20.4±6.59mV。进行了体外和体内实验以研究 PMBs 的药效和靶向药物输送。通过人脐静脉内皮细胞(HUVECs)的细胞活力评估细胞毒性,结果表明微泡即使在 2500mg/mL 的高浓度下也没有毒性,划痕愈合试验证明 PMBs 明显提高了 HUVECs 的迁移能力。此外,链脲佐菌素(STZ)联合高能量饮食用于构建 DCM 大鼠模型。血糖、胰腺和心脏的组织学变化以及心脏功能用于确证 DCM 大鼠模型的获得。PMBs 治疗组的组织学和生理学变化表明,与 DCM 模型组相比,PMBs 具有显著的治疗效果。因此,PMBs 是一种有前途的靶向药物输送系统和治疗 DCM 的新型非侵入性治疗方法。

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