草药干提取物 BNO 1011 改善慢性鼻-鼻窦炎兔模型的临床和黏液纤毛参数。
Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis.
机构信息
Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.
Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
出版信息
Int Forum Allergy Rhinol. 2019 Jun;9(6):629-637. doi: 10.1002/alr.22290. Epub 2019 Jan 18.
BACKGROUND
Enhancing chloride (Cl ) secretion in sinus epithelia represents a novel therapeutic approach to chronic rhinosinusitis (CRS). Herbal dry extract BNO 1011 enhances mucociliary clearance (MCC) via upregulation of Cl secretion in sinonasal cultures in vitro and murine epithelium in vivo. The objective of this study is to evaluate whether the BNO 1011 improves MCC and clinical parameters in a rabbit model of CRS.
METHODS
After the development of CRS in 30 New Zealand white rabbits, animals were randomly assigned to receive oral placebo (n = 10), BNO 1011 (low dose [LD], 25 mg/kg/daily) (n = 10), or BNO1011 (high dose [HD], 125 mg/kg/daily) (n = 10) for 4 weeks. Outcomes included sinus opacification (Kerschner's rabbit sinus CT grade), maxillary epithelial Cl secretion (sinus potential difference [PD] assay), airway surface liquid (ASL) depth using micro-optical coherence tomography (μOCT), and submucosal gland density (SMD) on histopathology. Outcome parameters were analyzed by 2 blinded investigators.
RESULTS
BNO 1011 significantly cleared sinus opacification (HD = 1.21 ± 0.63, LD = 1.26 ± 0.37,) compared to placebo (4.02 ± 0.92) (p = 0.009). BNO 1011 resulted in markedly greater mean sinus PD polarization (HD = -12.23 ± 1.4 mV, LD = -12.0 ± 3.0 mV) when compared to rabbits treated with placebo (-4.1 ± 1.1 mV) (p = 0.03). ASL depth was significantly improved when treated with HD (4.08 ± 0.06 μm) and LD (4.05 ± 0.06 μm) compared to placebo (3.5 ± 0.05 μm) (post hoc analysis, p < 0.0001). Histologically, epithelial thickness (HD = 10.0 ± 0.7 μm; LD = 13.7 ± 0.9 μm; placebo = 21.1 ± 2.3 μm; p < 0.005), subepithelial thickness (HD = 63.1 ± 6.6 μm; LD = 103.2 ± 6.7 μm; placebo = 113.3 ± 6.0 μm; p < 0.001), and SMD (HD = 22.2 ± 2.9%; LD = 31.8 ± 1.1%; placebo = 43.8 ± 1.7%; p < 0.0001) were noticeably better with the HD.
CONCLUSION
Herbal dry extract BNO 1011 improves radiographic, histologic, and MCC parameters in a rabbit model of CRS.
背景
增强窦上皮细胞中的氯离子（Cl-）分泌是治疗慢性鼻-鼻窦炎（CRS）的一种新方法。草药干提取物 BNO 1011 通过上调体外鼻-鼻窦培养物和体内鼠类上皮细胞中的 Cl-分泌，增强了黏液纤毛清除（MCC）功能。本研究旨在评估 BNO 1011 是否能改善 CRS 兔模型的 MCC 和临床参数。
方法
在 30 只新西兰白兔中建立 CRS 后，将动物随机分为接受口服安慰剂（n = 10）、低剂量 BNO 1011（25mg/kg/天）（n = 10）或高剂量 BNO1011（125mg/kg/天）（n = 10）治疗 4 周。结果包括窦腔混浊（Kerschner 兔窦 CT 分级）、上颌上皮 Cl-分泌（窦电位差[PD]测定）、气道表面液（ASL）深度（微光学相干断层扫描[μOCT]）和黏膜下腺密度（SMD）的组织病理学检查。两名盲法研究者对结果参数进行了分析。
结果
与安慰剂组（4.02 ± 0.92）相比，BNO 1011 可显著清除窦腔混浊（HD = 1.21 ± 0.63，LD = 1.26 ± 0.37）（p = 0.009）。与接受安慰剂治疗的兔子相比（-4.1 ± 1.1 mV），BNO 1011 导致的平均窦 PD 极化明显更大（HD = -12.23 ± 1.4 mV，LD = -12.0 ± 3.0 mV）（p = 0.03）。与安慰剂组（3.5 ± 0.05μm）相比，HD（4.08 ± 0.06μm）和 LD（4.05 ± 0.06μm）治疗的 ASL 深度显著改善（后验分析，p < 0.0001）。组织学上，上皮厚度（HD = 10.0 ± 0.7 μm；LD = 13.7 ± 0.9 μm；安慰剂 = 21.1 ± 2.3 μm；p < 0.005）、黏膜下厚度（HD = 63.1 ± 6.6 μm；LD = 103.2 ± 6.7 μm；安慰剂 = 113.3 ± 6.0 μm；p < 0.001）和 SMD（HD = 22.2 ± 2.9%；LD = 31.8 ± 1.1%；安慰剂 = 43.8 ± 1.7%；p < 0.0001）在接受 HD 治疗时明显更好。
结论
草药干提取物 BNO 1011 可改善 CRS 兔模型的影像学、组织学和 MCC 参数。
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