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负载辅酶Q10的脂质体联合超声介导微泡破坏技术可预防糖尿病大鼠早期肾病。

CoQ10-loaded liposomes combined with UTMD prevented early nephropathy of diabetic rats.

作者信息

Chen Pian-Pian, Xu He-Lin, ZhuGe De-Li, Jin Bing-Hui, Zhu Qun-Yan, Shen Bi-Xin, Wang Li-Fen, Lu Cui-Tao, Zhao Ying-Zheng, Li Xiao-Kun

机构信息

Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province, China.

The First Affiliated Hospital, Wenzhou Medical University, Wenzhou City, Zhejiang Province, China.

出版信息

Oncotarget. 2018 Jan 19;9(14):11767-11782. doi: 10.18632/oncotarget.24363. eCollection 2018 Feb 20.

Abstract

Nephropathy is one of the most severe complications of diabetic patients. The therapeutic strategies for diabetic patients should not only focus on the control of blood glucose but also pay attention to the occurrence of diabetic nephropathy (DN). Coenzyme Q10 (CoQ10) has great therapeutic potential for DN. However, the clinical application of CoQ10 has been limited because of its low water-solubility and non-specific distribution. Liposomes were supposed to be an effective way for delivering CoQ10 to kidney. CoQ10 was effectively encapsulated into the liposome (CoQ10-LIP) with a high entrapment efficiency of 86.15 %. The CoQ10-LIP exhibited a small hydrodynamic diameter (180 ± 2.1 nm) and negative zeta potential (-18.20 mV). Moreover, CoQ10-LIP was combined with ultrasound-mediated microbubble destruction (UTMD) to enhance specific distribution of CoQ10 in kidney. In early stage of diabetic mellitus (DM), rats were administrated with CoQ10-LIP followed by UTMD (CoQ10-LIP+UTMD) to prevent occurrence of DN. Results revealed that CoQ10-LIP+UTMD effectively prevented the renal morphology and function of diabetics rats from damage. The protective mechanism of CoQ10-LIP was highly associated with protecting podocyte, promoting vascular repair and inhibiting cell apoptosis. Conclusively, CoQ10-LIP in combination with UTMD might be a potential strategy to prevent occurrence of DN.

摘要

肾病是糖尿病患者最严重的并发症之一。糖尿病患者的治疗策略不仅应注重血糖控制,还应关注糖尿病肾病(DN)的发生。辅酶Q10(CoQ10)对DN具有巨大的治疗潜力。然而,由于其低水溶性和非特异性分布,CoQ10的临床应用受到限制。脂质体被认为是将CoQ10递送至肾脏的有效方式。CoQ10被有效地包封在脂质体(CoQ10-LIP)中,包封效率高达86.15%。CoQ10-LIP表现出较小的流体动力学直径(180±2.1nm)和负的zeta电位(-18.20mV)。此外,CoQ10-LIP与超声介导的微泡破坏(UTMD)相结合,以增强CoQ10在肾脏中的特异性分布。在糖尿病(DM)早期,给大鼠施用CoQ10-LIP,随后进行UTMD(CoQ10-LIP+UTMD)以预防DN的发生。结果显示,CoQ10-LIP+UTMD有效地防止了糖尿病大鼠的肾脏形态和功能受损。CoQ10-LIP的保护机制与保护足细胞、促进血管修复和抑制细胞凋亡高度相关。总之,CoQ10-LIP与UTMD联合应用可能是预防DN发生的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d8/5837748/6fd4acb11d69/oncotarget-09-11767-g001.jpg

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