| 摘要: |
| 目的：观察藿胆鼻渊丸对急性鼻窦炎大鼠炎症的影响及其分子机制。方法：将36只SD大鼠按随机数字表法分为正常组，模型组，阳性药物组，藿胆鼻渊丸低、中、高剂量组，每组各6只。采用鼻腔填塞联合鼻腔滴注脂多糖（LPS）法建立急性鼻窦炎大鼠模型。造模完成后，阳性药物组以阿莫西林克拉维酸钾（4∶1）干混悬剂灌胃（98.4375 g/kg），低、中、高剂量组予藿胆鼻渊丸灌胃（1.26 g/kg、2.52 g/kg、5.04 g/kg），正常组和模型组予0.9%氯化钠注射液灌胃，每只SD大鼠灌胃总体积为3 ml/次，2次/d，连续干预21 d。采用苏木精-伊红染色法（HE）观察大鼠鼻窦黏膜炎症变化；酶联免疫吸附法（ELISA）测定大鼠血清中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）含量；免疫组化（IHC）和蛋白质印迹法（WB）检测IL-1β、IL-6和TNF-α蛋白表达情况；WB检测HMGB1、TOLL样受体4重组蛋白（TLR4）、核转录因子-κB p65（NF-κB p65）和磷酸化NF-κB p65（p-NF-κB p65）蛋白表达情况。结果：与正常组比较，模型组鼻窦黏膜组织中炎症细胞浸润明显，阳性药物组和藿胆鼻渊丸不同剂量组炎症细胞聚集减少。与正常组比较，模型组血清中IL-1β、IL-6、TNF-α含量及IL-1β、IL-6、TNF-α蛋白表达均明显升高（P<0.05），鼻窦黏膜组织中的HMGB1、TLR4、NF-κB p65和p-NF-κB p65蛋白表达均明显升高（P<0.05）。与模型组比较，阳性药物组、藿胆鼻渊丸不同剂量组血清中IL-1β、IL-6、TNF-α含量及IL-1β、IL-6、TNF-α蛋白表达均明显降低（P<0.05），鼻窦黏膜组织中的HMGB1、TLR4、NF-κB p65和p-NF-κB p65蛋白表达均下降（P<0.05）。与阳性药物组比较，高剂量组IL-1β、IL-6、TNF-α含量及IL-1β、IL-6、TNF-α蛋白表达均明显降低（P<0.05），HMGB1、TLR4、NF-κB p65和p-NF-κB p65蛋白表达下降（P<0.05）。结论：藿胆鼻渊丸可以有效抑制急性鼻窦炎大鼠炎症反应，其机制可能是通过下调HMGB1分子，抑制TLR4/NF-κB信号通路，减少IL-1β、IL-6和TNF-α释放，从而达到抑制炎症的作用。 |
| 关键词: 急性鼻窦炎 藿胆鼻渊丸 HMGB1/TLR4/NF-κB |
| DOI： |
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| Effect of Huodan Biyuan pills in inhibiting inflammatory response in rats with acute sinusitis based on the high-mobility group box 1/Toll-like receptor 4/nuclear factor-kappa B pathway |
| XIONG Jing,WU Ting,LAN Chao |
| (Yueyang Hospital of Traditional Chinese Medicine，Yueyang 414000，Hunan，China) |
| Abstract: |
| Objective：To investigate the effect of Huodan Biyuan pills on inflammation in rats with acute sinusitis and its molecular mechanism.Methods：A total of 36 Sprague-Dawley rats were divided into normal group，model group，positive drug group，and low-，middle-，high-dose Huodan Biyuan pills groups using a random number table，with 6 rats in each group.Nasal cavity occlusion combined with nasal dripping of lipopolysaccharide were performed to establish a rat model of acute sinusitis.After modeling，the rats in the positive drug group were given the dry suspension of amoxicillin and clavulanate potassium (4∶1) at a dose of 98.4375 g/kg by gavage；the rats in the low-，middle-，high-dose Huodan Biyuan pills groups were given Huodan Biyuan pills by gavage at a dose of 1.26 g/kg，2.52 g/kg，and 5.04 g/kg，respectively；the rats in the normal group and the model group were given 0.9% sodium chloride by gavage at a volume of 3 mL each time，twice a day for 21 consecutive days.HE staining was used to observe the inflammatory changes of sinus mucosa；ELISA was used to measure the serum levels of interleukin-1β (IL-1β)，interleukin-6 (IL-6)，and tumor necrosis factor-α (TNF-α)，and immunohistochemistry and Western blotting were used to measure the protein expression levels of IL-1β，IL-6，TNF-α；Western blotting was used to measure the protein expression levels of high-mobility group box 1 (HMGB1)，Toll-like receptor 4 (TLR4)，nuclear factor-kappa B p65 (NF-κB p65)，and phosphorylated NF-κB p65 (p-NF-κB p65).Results：Compared with the normal group，the model group had significant inflammatory cell infiltration in sinus mucosa，while the positive drug group and the Huodan Biyuan pills groups had a reduction in inflammatory cell infiltration.Compared with the normal group，the model group had significant increases in the serum levels and protein expression levels of IL-1β，IL-6，and TNF-α (P<0.05)，as well as significant increases in the protein expression levels of HMGB1，TLR4，NF-κB p65，and p-NF-κB p65 in sinus mucosa (P<0.05).Compared with the model group，the positive drug group and the Huodan Biyuan pills groups had significant reductions in the serum levels and protein expression levels of IL-1β，IL-6，and TNF-α (P<0.05)，as well as significant reductions in the protein expression levels of HMGB1，TLR4，NF-κB p65，and p-NF-κB p65 in sinus mucosa (P<0.05).Compared with the positive drug group，the high-dose Huodan Biyuan pills group had significant reductions in the serum levels and protein expression levels of IL-1β，IL-6，and TNF-α (P<0.05)，as well as significant reductions in the protein expression levels of HMGB1，TLR4，NF-κB p65，and p-NF-κB p65 (P<0.05).Conclusion：Huodan Biyuan pills can effectively inhibit inflammatory response in rats with acute sinusitis，possibly by downregulating HMGB1，inhibiting the TLR4/NF-κB signaling pathway，and reducing the release of IL-1β，IL-6，and TNF-α. |
| Key words: acute sinusitis Huodan Biyuan pills high-mobility group box 1/Toll-like receptor 4/nuclear factor-kappa B |
