中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (3): 537-542.doi: 10.4103/1673-5374.293155

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

携带姜黄素和地塞米诺松固体脂质纳米颗粒治疗重度抑郁症

  

  • 出版日期:2021-03-15 发布日期:2020-12-17
  • 基金资助:

    中国国家自然科学基金项目(816711058187399431727801),中国国家重点研究发展计划项目(2016YFA0100800)和国家自然科学基金国际合作项目(81820108013

Solid lipid nanoparticles loading with curcumin and dexanabinol to treat major depressive disorder

Xiao-Lie He, Li Yang, Zhao-Jie Wang, Rui-Qi Huang, Rong-Rong Zhu*, Li-Ming Cheng*   

  1. Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Science and Technology, Tongji University, Shanghai, China
  • Online:2021-03-15 Published:2020-12-17
  • Contact: Li-Ming Cheng, limingcheng@tongji.edu.cn; Rong-Rong Zhu, rrzhu@tongji.edu.cn.
  • Supported by:
    This work was financially supported by the National Natural Science Foundation of China, Nos. 81671105, 81873994, 31727801 (to RRZ), the National Key Research and Development Program of China, No. 2016YFA0100800 (to LMC), and the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China, No. 81820108013 (to LMC).

摘要:

地塞米诺是一种人工合成的大麻素衍生物,可通过抗炎和抗氧化作用,发挥其神经保护作用。姜黄素对重度抑郁症具有抗抑郁作用。为证实携带姜黄素和地塞米诺的功能化固体脂质纳米颗粒(Cur/SLNs-HU-211)的抗抑郁作用效果并研究其作用机制,实验通过连续21d腹腔注射皮质酮分别建立了野生型(CB1+/+)与大麻素受体1敲除(CB1-/-)重度抑郁症小鼠模型,然后连续2周腹腔注射携带姜黄素和地塞米诺的功能化固体脂质纳米颗粒(含姜黄素20 mg/kg)进行治疗。结果发现,携带姜黄素和地塞米诺的功能化固体脂质纳米颗粒可增加CB1+/+重度抑郁症小鼠模型海马和纹状体成熟神经元标记物NeuN,MAP2和Tuj1基因及蛋白表达,促进海马和纹状体中多巴胺和去甲肾上腺素的释放,并提高海马和纹状体中大麻素1及其下游Rasgef1c和Egr1 mRNA的表达,同时明显改善小鼠的神经功能;但是这种纳米颗粒对CB1-/-小鼠抑郁模型无效。说明Cur/SLNs-HU-211可能通过大麻素受体1相关信号通路对重度抑郁症发挥治疗作用。实验于2017年5月24日经同济大学附属同济医院伦理委员会批准,批准号2017-DW-020。

https://orcid.org/0000-0003-3396-4300 (Li-Ming Cheng); 

https://orcid.org/0000-0002-3955-5965 (Rong-Rong Zhu)

关键词: 抑郁, 纳米颗粒, 姜黄素, 地塞那醇, 多巴胺, 去甲肾上腺素, 生物相容性

Abstract: Dexanabinol (HU-211) is an artificially synthesized cannabinoid derivative that exerts neuroprotective effects through anti-inflammatory and antioxidant effects. Curcumin exhibits antidepressant effects in the treatment of major depressive disorder. To investigate the antidepressant effects of solid lipid nanoparticles loaded with both curcumin and dexanabinol, and the underlying mechanisms associated with this combination, we established wild-type (CBR1+/+) and cannabinoid receptor 1 (CBR1) knockout (CBR1–/–) mouse models of major depressive disorder, through the intraperitoneal injection of corticosterone, for 3 successive days, followed by treatment with intraperitoneal injections of solid lipid nanoparticles loading with curcumin (20 mg/kg) and dexanabinol (0.85 mg/kg), for 2 successive days. Our results revealed that solid lipid nanoparticle loading with curcumin and dexanabinol increased the mRNA and protein expression levels of the mature neuronal markers neuronal nuclei, mitogen-activated protein 2, and neuron-specific beta-tubulin III, promoted the release of dopamine and norepinephrine, and increased the mRNA expression of CBR1 and the downstream genes Rasgef1c and Egr1, and simultaneously improved rat locomotor function. However, solid lipid nanoparticles loaded with curcumin and dexanabinol had no antidepressant effects on the CBR1–/– mouse models of major depressive disorder. This study was approved by the Institutional Ethics Committee of Tongji Hospital of Tongji University, China (approval No. 2017-DW-020) on May 24, 2017.

Key words: biocompatibility, curcumin, depression, dexanabinol, dopamine, nanoparticles, norepinephrine