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海藻酸钠寡糖纳米药物通过下调血清miR-155改善骨质疏松症患者后路腰椎椎间融合器融合治疗退行性腰椎疾病的疗效。

Oligosaccharide nanomedicine of alginate sodium improves therapeutic results of posterior lumbar interbody fusion with cages for degenerative lumbar disease in osteoporosis patients by downregulating serum miR-155.

作者信息

Qu Yang, Wang Zhengming, Zhou Haohan, Kang Mingyang, Dong Rongpeng, Zhao Jianwu

机构信息

Department of Orthopedics, The Second Hospital of Jilin University, Changchun, People's Republic of China.

出版信息

Int J Nanomedicine. 2017 Nov 24;12:8459-8469. doi: 10.2147/IJN.S143824. eCollection 2017.

DOI:10.2147/IJN.S143824
PMID:29200854
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5703176/
Abstract

Degenerative lumbar disease (DLD) is a significant issue for public health. Posterior lumbar intervertebral fusion with cages (PLIFC) has high-level fusion rate and realignment on DLD. However, there are some complications following the surgery. Alginate oligosaccharides (AOS) have antioxidant and anti-inflammatory activities and may be suitable for infection therapy. MiR-155 is a biomarker associated with inflammatory and oxidative stress. AOS may promote PLIFC therapy by regulating miR-155. Pluronic nanoparticles and oligosaccharide nanomedicine of alginate sodium (ONAS) were prepared with ampicillin at size <200 nm. Ninety-six DLD osteoporosis patients received PLIFC and were evenly assigned into ONAS group (OG, oral administration of 100 mg ONAS daily) and control group (PG, 100 mg pluronic nanoparticles). Serum miR-155 level was measured by real-time quantitative PCR. The levels of superoxide dismutase (SOD), glutathione (GSH), aspartate aminotransaminase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β), and interleukin-1 receptor antagonist (IL-1ra) were measured. Weighted mean difference (WMD), relative risk (RR), complications, surgery infection rate, fusion rate, and Japanese Orthopaedic Association (JOA) scores were used to evaluate therapeutic efficacy. After 1-month therapy, infection rates and side effects were lower in OG than those in PG (RR =0.64, 95% confidence interval [CI] [0.48, 0.84], =0.001). The fusion rates were higher in OG than in PG (WMD =21.96, 95% CI [-0.24, 37.62], =0.021). The JOA scores were higher in OG than in PG (RR =0.52, 95% CI [0.33, 0.84], =0.007), and no significant difference was found for the visual analog scale and Oswestry Disability Index. Serum levels of miR-155, ALT, AST, and IL-1β were lower while SOD, GSH, and IL-1ra were higher in OG than in PG. MiR-155 mimic increased the levels of ALT, AST, and IL-1β and reduced the levels of SOD, GSH, and IL-1ra. In contrast, miR-155 inhibitor had reverse results. Therefore, ONAS has better improvement in complications and therapeutic effects on DLD by regulating serum miR-155.

摘要

退行性腰椎疾病(DLD)是一个重大的公共卫生问题。后路腰椎椎间融合器融合术(PLIFC)对DLD具有较高的融合率和复位效果。然而,该手术后存在一些并发症。海藻酸盐寡糖(AOS)具有抗氧化和抗炎活性,可能适用于感染治疗。MiR-155是一种与炎症和氧化应激相关的生物标志物。AOS可能通过调节MiR-155促进PLIFC治疗。用氨苄青霉素制备了尺寸小于200nm的普朗尼克纳米颗粒和海藻酸钠寡糖纳米药物(ONAS)。96例DLD骨质疏松患者接受了PLIFC手术,并被平均分为ONAS组(OG,每日口服100mg ONAS)和对照组(PG,100mg普朗尼克纳米颗粒)。通过实时定量PCR测量血清MiR-155水平。测量超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、白细胞介素-1β(IL-1β)和白细胞介素-1受体拮抗剂(IL-1ra)的水平。采用加权平均差(WMD)、相对风险(RR)、并发症、手术感染率、融合率和日本矫形外科学会(JOA)评分来评估治疗效果。治疗1个月后,OG组的感染率和副作用低于PG组(RR =0.64,95%置信区间[CI][0.48,0.84],P =0.001)。OG组的融合率高于PG组(WMD =21.96,95%CI[-0.24,37.62],P =0.021)。OG组的JOA评分高于PG组(RR =0.52,95%CI[0.33,0.84],P =0.007),视觉模拟评分和Oswestry功能障碍指数无显著差异。OG组血清MiR-155、ALT、AST和IL-1β水平较低,而SOD、GSH和IL-1ra水平较高。MiR-155模拟物增加了ALT、AST和IL-1β水平,降低了SOD、GSH和IL-1ra水平。相反,MiR-155抑制剂则产生相反的结果。因此,ONAS通过调节血清MiR-155对DLD的并发症和治疗效果有更好的改善作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/facc/5703176/ab6f221a16d7/ijn-12-8459Fig7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/facc/5703176/faf6df196303/ijn-12-8459Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/facc/5703176/1ddd415fe210/ijn-12-8459Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/facc/5703176/fc01087358e8/ijn-12-8459Fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/facc/5703176/ab6f221a16d7/ijn-12-8459Fig7.jpg

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