人神经干细胞分泌组改善脊髓损伤大鼠模型神经性疼痛和运动功能的机制:通过抗氧化、抗炎、抗基质降解和神经营养活性。

IF 3.4 3区医学 Q2 CLINICAL NEUROLOGY Korean Journal of Pain Pub Date : 2023-01-01 DOI:10.3344/kjp.22279

I Nyoman Semita, Dwikora Novembri Utomo, Heri Suroto, I Ketut Sudiana, Parama Gandi

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引用次数: 3

摘要

背景:在全球范围内，脊髓损伤(SCI)造成了很大的负担，其中90%的人患有永久性残疾，60%-69%的人患有神经性疼痛。主要原因是氧化应激、炎症和变性。干细胞分泌组的疗效是有希望的，但人类神经干细胞分泌组在神经性疼痛中的作用尚不清楚。本研究评估了hnsc分泌组通过抗氧化、抗炎、抗基质降解和神经营养活性改善脊髓损伤大鼠模型神经性疼痛和运动功能的机制。方法:将15只褐家鼠分为正常组、对照组和治疗组(hnsc -分泌组30 μL，鞘内T10水平，创伤性脊髓损伤后3 d)。损伤后28 d采集标本，检测基质金属蛋白酶(MMP)-9、f2 -异前列腺素、肿瘤坏死因子(TNF)-α、转化生长因子(TGF)-β、脑源性神经营养因子(BDNF)水平。通过Basso、Beattie和Bresnahan评分评估运动恢复情况。神经性疼痛采用大鼠鬼脸量表进行评估。结果:hnsc分泌组能改善运动恢复和神经性疼痛，降低f2 -异前列腺素(抗氧化)，降低MMP-9和TNF-α(抗炎)，调节TGF-β和BDNF(神经营养因子)。此外，HNSC-secretomes通过降低MMP-9的基质降解作用和增加TGF-β的胶原形成作用来维持SCI的细胞外基质，从而成为胶质瘢痕形成的阻力。结论:本研究揭示了hnsc分泌组通过抗氧化、抗炎、抗基质降解和神经营养活性改善脊髓损伤神经性疼痛和运动功能的机制。

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The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 μL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale.

Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation.

Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

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来源期刊

Korean Journal of Pain Medicine-Anesthesiology and Pain Medicine

CiteScore

5.40

自引率

7.10%

发文量

审稿时长

16 weeks

期刊介绍： Korean Journal of Pain (Korean J Pain, KJP) is the official journal of the Korean Pain Society, founded in 1986. It has been published since 1988. It publishes peer reviewed original articles related to all aspects of pain, including clinical and basic research, patient care, education, and health policy. It has been published quarterly in English since 2009 (on the first day of January, April, July, and October). In addition, it has also become the official journal of the International Spinal Pain Society since 2016. The mission of the Journal is to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals. The circulation number per issue is 50.