Song Zhaojun, Wang Zhigang, Shen Jieliang, Xu Shengxi, Hu Zhenming
Department of Orthopedics, The First Affiliated Hospital.
Institution of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Int J Nanomedicine. 2017 Mar 2;12:1717-1729. doi: 10.2147/IJN.S128848. eCollection 2017.
Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory.
This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (/PLGA NBs) on nerve regeneration in rats following SCI.
Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, and NBs group, and US group, and /PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test.
therapy using US-mediated /PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI.
US-mediated /PLGA NBs destruction effectively transfects the gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through /PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases.
脊髓损伤(SCI)可导致严重残疾或死亡。治疗选择包括手术干预、药物治疗和干细胞移植。然而,这些方法在功能恢复方面的疗效仍不尽人意。
本研究旨在探讨超声(US)介导破坏表达神经生长因子(NGF)的聚乳酸-羟基乙酸共聚物(PLGA)纳米气泡(NBs)(/PLGA NBs)对脊髓损伤大鼠神经再生的影响。
建立Allen打击模型的脊髓损伤成年雄性Sprague Dawley大鼠随机分为四个治疗组。分组为生理盐水(NS)组、NBs组、US组、/PLGA NBs与US组。通过苏木精和伊红染色观察脊髓损伤后的组织学变化。用尼氏染色法测定神经元活力。采用末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记染色检测细胞凋亡。通过定量逆转录聚合酶链反应和蛋白质印迹法检测NGF基因和蛋白表达。使用倒置荧光显微镜检查脊髓中的绿色荧光蛋白表达。使用Basso、Beattie和Bresnahan试验测定神经功能恢复情况。
US介导的/PLGA NBs破坏疗法显著增加了NGF表达,减轻了组织学损伤,减少了神经元丢失,抑制了脊髓损伤大鼠损伤脊髓中的神经元凋亡,并提高了BBB评分。
US介导的/PLGA NBs破坏可有效地将 基因转染到靶组织中,对损伤脊髓有显著影响。US照射与通过/PLGA NBs进行基因治疗的联合应用在纳米医学的未来以及脊髓损伤和其他疾病的无创治疗选择的发展方面具有巨大潜力。