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新风胶囊通过NF-ΚB-iNOS-NO信号通路改善强直性脊柱炎患者的肺功能。

Xinfeng capsule improves pulmonary function in ankylosing spondylitis patients via NF-ΚB-iNOS-NO signaling pathway.

作者信息

Liu Jian, Qi Yajun, Zheng Li, Cao Yunxiang, Wan Lei, Ye Wenfang, Fang Li

出版信息

J Tradit Chin Med. 2014 Dec;34(6):657-65. doi: 10.1016/s0254-6272(15)30079-0.

DOI:10.1016/s0254-6272(15)30079-0
PMID:25618969
Abstract

OBJECTIVE

To study changes in the nuclear factor-κB p65 (NF-κB p65)-inducible nitric oxide synthase (iNOS)-nitric oxide (NO) signaling pathway and the effects of Xinfeng capsules (XFC) in patients with ankylosing spondylitis (AS).

METHODS

One hundred twenty patients with AS were randomly divided into an XFC group and a Salazopyrin group. Sixty health subjects were included as a normal control group. In the two treatment groups, pulmonary functional parameters, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), maximal voluntary ventilation (MVV), peak expiratory flow (PEF), forced expiratory flow at 25% of forced vital capacity (FEF25), forced expiratory flow at 50% of forced vital capacity (FEF50), and forced expiratory flow at 75% of forced vital capacity (FEF75) were determined. Enzyme linked immunosorbent assays were used for detection of the serum oxidative stress indexes, NF-κB p65, iNOS, NO, reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidative capacity (TAOC) and interleukin-4 (IL-4), IL-10, IL-1β, and tumor necrosis factor-α (TNF-α) contents. Westergren's method was used for determination of erythrocyte sedimentation rate (ESR). High-sensitivity C-reactive protein (Hs-CRP) was detected with a 7060 full-automatic biochemical analyzer (Hitachi, Japan).

RESULTS

The clinical therapeutic effect in the XFC group was significantly superior to that in the Salazopyrin group (P < 0.01). Compared with the normal control group, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT, TAOC, IL-4, IL-10 were significantly lower, and NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-1β, TNF-α, ESR, and Hs-CRP significantly higher in patients with AS (P < 0.01 or P < 0.05). Compared with before treatment, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT, TAOC, IL-4, and IL-10 were significantly increased, and NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-1β, TNF-α, ESR, CRP, visual analog scales (VAS), Bath ankylosing spondylitis disease active index, Bath ankylosing spondylitis functional index, and Bath ankylosing spondylitis global index significantly decreased in the two treatment groups after treatment (P <. 0.01 or P < 0.05), with significant differences between the XFC and Salazopyrin groups (P < 0.01 or P < 0.05). Spearman correlation analysis indicated that FEV1, MWVV, PEF, FEF50, and FEF75 were positively correlated with SOD, CAT, TAOC, IL-4, and IL-10, and were negatively correlated with NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-13, TNF-α, ESR, and CRP.

CONCLUSION

Patients with AS have local pathologic changes in the spinal cord and other joints. They also have decreased pulmonary function, which is negatively correlated with the NF-κB-iNOS-NO signaling pathway, oxidative indexes, and inflammatory factors. XFC improves rigidity and pain in spinal joints and other symptoms, laboratory indexes, and pulmonary function. The mechanism is possibly related to inhibition of the NF-KB-iNOS-NO signaling pathway.

摘要

目的

研究核因子-κB p65(NF-κB p65)-诱导型一氧化氮合酶(iNOS)-一氧化氮(NO)信号通路的变化以及新风胶囊(XFC)对强直性脊柱炎(AS)患者的影响。

方法

将120例AS患者随机分为XFC组和柳氮磺胺吡啶组。纳入60名健康受试者作为正常对照组。测定两个治疗组的肺功能参数,包括用力肺活量(FVC)、第1秒用力呼气量(FEV1)、最大自主通气量(MVV)、呼气峰值流速(PEF)、用力肺活量25%时的用力呼气流量(FEF25)、用力肺活量50%时的用力呼气流量(FEF50)和用力肺活量75%时的用力呼气流量(FEF75)。采用酶联免疫吸附测定法检测血清氧化应激指标、NF-κB p65、iNOS、NO、活性氧(ROS)、活性氮(RNS)、丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、总抗氧化能力(TAOC)以及白细胞介素-4(IL-4)、IL-10、IL-1β和肿瘤坏死因子-α(TNF-α)的含量。采用魏氏法测定红细胞沉降率(ESR)。使用7060全自动生化分析仪(日本日立公司)检测高敏C反应蛋白(Hs-CRP)。

结果

XFC组的临床治疗效果显著优于柳氮磺胺吡啶组(P < 0.01)。与正常对照组相比,AS患者的FEV1、MVV、PEF、FEF50、FEF75、SOD、CAT、TAOC、IL-4、IL-10显著降低,而NF-κB p65、iNOS、NO、ROS、RNS、MDA、IL-1β、TNF-α、ESR和Hs-CRP显著升高(P < 0.01或P < 0.05)。与治疗前相比,两个治疗组治疗后FEV1、MVV、PEF、FEF50、FEF75、SOD、CAT、TAOC、IL-4和IL-10显著升高,而NF-κB p65、iNOS、NO、ROS、RNS、MDA、IL-1β、TNF-α、ESR、C反应蛋白(CRP)、视觉模拟评分(VAS)、巴斯强直性脊柱炎疾病活动指数、巴斯强直性脊柱炎功能指数和巴斯强直性脊柱炎综合指数显著降低(P < 0.01或P < 0.05),XFC组和柳氮磺胺吡啶组之间存在显著差异(P < 0.01或P < 0.05)。Spearman相关性分析表明,FEV1、MWVV、PEF、FEF50和FEF75与SOD、CAT、TAOC、IL-4和IL-10呈正相关,与NF-κB p65、iNOS、NO、ROS、RNS、MDA、IL-13、TNF-α、ESR和CRP呈负相关。

结论

AS患者脊髓和其他关节存在局部病理改变。他们的肺功能也有所下降,这与NF-κB-iNOS-NO信号通路、氧化指标和炎症因子呈负相关。XFC可改善脊柱关节的僵硬和疼痛以及其他症状、实验室指标和肺功能。其机制可能与抑制NF-KB-iNOS-NO信号通路有关。

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