中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (9): 2043-2049.doi: 10.4103/1673-5374.335160

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

释放一氧化氮的硅纳米颗粒促进急性周围神经压迫损伤后血管重建和功能恢复

  

  • 出版日期:2022-09-15 发布日期:2022-03-08

Delivery of nitric oxide-releasing silica nanoparticles for in vivo revascularization and functional recovery after acute peripheral nerve crush injury

Jung Il Lee1, #, Ji Hun Park1, #, Yeong-Rim Kim2, Kihak Gwon2, Hae Won Hwang3, 4, Gayoung Jung3, Joo-Yup Lee5, Jeong-Yun Sun4, Jong Woong Park1, *, Jae Ho Shin2, 6, *, Myoung-Ryul Ok3, *   

  1. 1Department of Orthopedic Surgery, College of Medicine, Korea University, Seoul, Republic of Korea; 2Medical Sensor Biomaterial Research Institute, Kwangwoon University, Seoul, Republic of Korea; 3Center for Biomaterials, Korea Institute of Science & Technology, Seoul, Republic of Korea; 4Department of Materials Science and Engineering, Seoul National University, Seoul, Republic of Korea; 5Department of Orthopedic Surgery, College of Medicine, Catholic University, Seoul, Republic of Korea; 6Department of Chemistry, Kwangwoon University, Seoul, Republic of Korea
  • Online:2022-09-15 Published:2022-03-08
  • Contact: Jong Woong Park, MD, PhD, ospark@korea.ac.kr; Jae Ho Shin, PhD, jhshin@kw.ac.kr; Myoung-Ryul Ok, PhD, omr2da@kist.re.kr.
  • Supported by:
    This work was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT, Nos. NRF-2015R1C1A1A02036830 (to JIL) and NRF-2015M3A9E2029186 (to JHS). This work was also supported by a grant of the Korea Institute of Science and Technology, Nos. 2V05460/2V08630 (KIST-KU TRC program), 2E31121 (to MRO) and a grant of Korea University Anam Hospital (to JHP and JWP).

PDF

45

摘要：

一氧化氮已被证明可以促进周围神经损伤（PNI）后的血管再生和神经再生。然而，由于缺乏能够储存大量一氧化氮分子并在临床上有意义的时间范围内释放的稳定载体材料，一氧化氮的体内应用仍然具有挑战性。最近，一种能够以可控和持续的速度储存和释放一氧化氮的二氧化硅纳米粒子系统引起研究者的关注。实验将释放一氧化氮的二氧化硅纳米颗粒与天然水凝胶混合后递送到大鼠急性挤压伤后的周围神经，以确保一氧化氮有效地应用到病变部位。使用聚合物染料进行微血管造影和免疫组化染色检测CD34（血管重塑的标志物）结果显示，释放一氧化氮的二氧化硅纳米颗粒的递送使坐骨神经压伤部位的血管重建数量有所增加。坐骨神经功能指数和组织解剖学检查显示，经一氧化氮治疗的大鼠坐骨神经功能和肌肉功能明显改善，损伤坐骨神经中的有髓轴突的数量和湿肌肉重量都有所增加。研究结果表明，在急性坐骨神经损伤后，向损伤部位递送一氧化氮会触发病变处的血管重建增强，并促进轴突再生及改善功能恢复。

https://orcid.org/0000-0003-2751-2519 (Jong Woong Park); https://orcid.org/0000-0002-6117-6910 (Jae Ho Shin); 
https://orcid.org/0000-0003-2733-9074 (Myoung-Ryul Ok)

Abstract: Nitric oxide (NO) has been shown to promote revascularization and nerve regeneration after peripheral nerve injury. However, in vivo application of NO remains challenging due to the lack of stable carrier materials capable of storing large amounts of NO molecules and releasing them on a clinically meaningful time scale. Recently, a silica nanoparticle system capable of reversible NO storage and release at a controlled and sustained rate was introduced. In this study, NO-releasing silica nanoparticles (NO-SNs) were delivered to the peripheral nerves in rats after acute crush injury, mixed with natural hydrogel, to ensure the effective application of NO to the lesion. Microangiography using a polymer dye and immunohistochemical staining for the detection of CD34 (a marker for revascularization) results showed that NO-releasing silica nanoparticles increased revascularization at the crush site of the sciatic nerve. The sciatic functional index revealed that there was a significant improvement in sciatic nerve function in NO-treated animals. Histological and anatomical analyses showed that the number of myelinated axons in the crushed sciatic nerve and wet muscle weight excised from NO-treated rats were increased. Moreover, muscle function recovery was improved in rats treated with NO-SNs. Taken together, our results suggest that NO delivered to the injured sciatic nerve triggers enhanced revascularization at the lesion in the early phase after crushing injury, thereby promoting axonal regeneration and improving functional recovery. 

Key words: crush injury, nerve injury, nerve regeneration, nitric oxide, peripheral nerve, revascularization, silica nanoparticles