文章摘要
张瑞芹,胡云磊,王芳,闫保星.基于HMGB1/TLR4/NF-κB信号通路研究木兰脂素对急性鼻窦炎大鼠的治疗作用及机制[J].中国药事,2022,36(5):526-534
基于HMGB1/TLR4/NF-κB信号通路研究木兰脂素对急性鼻窦炎大鼠的治疗作用及机制
Therapeutic Effects and Mechanism of Magnolidin Against Acute Sinusitis in Rats Based on HMGB1/TLR4/NF- κB Signaling Pathway
  
DOI:10.16153/j.1002-7777.2022.05.006
中文关键词: 急性鼻窦炎  木兰脂素  高迁移率家族蛋白1  Toll样受体4  核因子-κB  信号通路  大鼠
英文关键词: acute sinusitis  magnolidin  high-mobility family proteins 1  Toll-like receptor 4  nuclear factor-κB  signaling pathway  rats
基金项目:河南省医学科技攻关计划项目(编号 LHGJ20191016)
作者单位
张瑞芹 信阳市中心医院,信阳 464000 
胡云磊 信阳市中心医院,信阳 464000 
王芳 信阳市中心医院,信阳 464000 
闫保星 郑州市第二人民医 院,郑州 450015 
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中文摘要:
      目的: 观察木兰脂素对急性鼻窦炎(ARS)大鼠的治疗作用,并探讨其通过高迁移率家族蛋白1/ Toll样受体4/核因子-κB(HMGB1/TLR4/NF-κB)信号通路的调控机制方法: 49只大鼠,随机取9 只作为正常组,40只用鼻窦腔内接种金黄色葡萄球菌法制备ARS模型,36只建模成功大鼠随机分为模型组、木兰脂素低剂量组、木兰脂素高剂量组、阳性组,各9只。木兰脂素低剂量组、木兰脂素高剂量组分别灌胃20、80 mg·kg-1体质量的木兰脂素,模型组和正常组灌胃等体质量溶媒,阳性组灌胃40 mg·kg-1 体质量左氧氟沙星,连续7 d。给药前、末次给药后1 h评估各组鼻窦炎症状评分;测定给药后各组血白细胞(WBC)计数及中性粒细胞占比,观察鼻窦黏膜病理组织学变化,检测鼻腔灌洗液中肿瘤坏死因子-α(TNF-α)、白介素(IL)-6水平及鼻黏膜中HMGB1、TLR4、NF-κB mRNA和蛋白表达情况结果: 给药后,木兰脂素低剂量组、高剂量组、阳性组的急性鼻窦炎症状评分及血WBC计数均低于模型组,但仍高于正常组,且木兰脂素高剂量组及阳性组均低于木兰脂素低剂量组,差异均有统计学意义(P<0.05),而木兰脂素高剂量组与阳性组比较,差异无统计学意义(P>0.05)。与给药前比较,给药后木兰脂素低剂量组、高剂量组及阳性组急性鼻窦炎症状评分均降低(P<0.05),正常组及模型组给药前后无明显差异(P>0.05)。与模型组比较,木兰脂素低剂量组、木兰脂素高剂量组、阳性组中性粒细胞占比均降低,且木兰脂素高剂量组低于木兰脂素低剂量组,阳性组低于木兰脂素高剂量组,差异均有统计学意义(P<0.05),而阳性组与正常组比较,差异无统计学意义(P>0.05)。HE染色显示,模型组大鼠纤毛脱落、缺失、排列紊乱,黏膜上皮破损、变性,黏膜内及黏膜下可见大量炎症细胞浸润; 木兰脂素低剂量组、木兰脂素高剂量组及阳性组上述病理变化均减轻,且木兰脂素高剂量组和阳性组炎症反应减轻更为明显。与模型组比较,木兰脂素低剂量组、木兰脂素高剂量组、阳性组鼻腔灌洗液中 TNF-α、IL-6水平及鼻黏膜中HMGB1、TLR4、NF-κB mRNA和蛋白相对表达量均降低,但仍高于正常组,且木兰脂素高剂量组及阳性组均低于木兰脂素低剂量组,差异均有统计学意义(P<0.05),而木兰脂素高剂量组及阳性组比较,差异无统计学意义(P>0.05)结论: 木兰脂素治疗ARS效果显著,可能通过HMGB1/TLR4/NF-κB信号通路抑制鼻黏膜炎症反应。
英文摘要:
      Objective: To observe the therapeutic effect of magnolidin against acute rhinosinusitis (ARS) in rats, and investigate its regulatory mechanism through the high-mobility family proteins 1/Toll-like receptor 4/nuclear factor-κB (HMGB1/TLR4/NF-κB) signaling pathway. Methods: Nine rats were randomly selected from 49 rats as the normal group. Forty rats were prepared by intranasal sinus inoculation with staphylococcus aureus to make ARS model. 36 successfully modeled rats were randomly divided into the model group, the magnolidin low-dose group, the magnolidin high-dose group and the positive group, with nine rats in each group. The rats in the magnolidin low-dose and high-dose groups were intragastrated with 20 and 80 mg·kg-1 body mass of magnolian respectively, the rats in the model group and the normal group were administrated with the equal volume of vehicle, and the rats in the positive group were given 40 mg·kg-1 body mass of levofloxacin for 7 days in a row. The symptom scores of nasosinusitis in each group before administration and 1 hour after the last administration were evaluated. After administration, the white blood cell (WBC) count and the proportion of neutrophils were measured, the histopathological changes of the nasal sinus mucosa were observed and the levels of TNF-α and IL-6 in nasal lavage fluid and the expressions of HMGB1, TLR4, NF-κB mRNA and proteins in nasal mucosa were detected. Results: After administration, the acute sinusitis symptom scores and blood WBC count in the magnolidin low-dose and high-dose groups and the positive group were lower than those of the model group, but they were still higher than those of the normal group. The scores and the count in magnolidin high-dose group and the positive group were lower than those in low-dose group. The difference was statistically significant (P<0.05), while there was no significant difference between the magnolidin high-dose group and the positive group (P>0.05). Compared with the scores before administration, the acute sinusitis symptom scores in magnolidin low-dose and high-dose groups and the positive group after administration had all decreased (P<0.05), while there was no significant difference in the normal group and model group before and after administration (P>0.05). Compared with that of the model group, the proportion of neutrophils in the magnolidin low-dose and high-dose groups and the positive group had decreased. The proportion in the high-dose group was lower than that in the low-dose group, and the proportion in the positive group was lower than that in the high-dose group. The difference was statistically significant (P<0.05), while there was no significant difference between the positive group and the normal group (P>0.05). HE staining showed that the rat cilia of the model group were exfoliated or missing or arranged disorderly, the mucosal epithelium was damaged or degenerated and a large number of inflammatory cells inside and below the mucosa were infiltrated. The pathological changes in the magnolidin low-dose and high-dose groups and positive group all reduced. In addition, the inflammatory response in the magnolidin high-dose group and positive group was even obvious. Compared with those of the model group, the levels of TNF-α and IL-6 in the nasal lavage fluid and the relative expressions of HMGB1, TLR4, NF-κB mRNA and proteins in the nasal mucosa of the low-dose group, high-dose group and positive group of mularin had all decreased, but they were higher than those of the normal group. Those in the magnolidin high-dose group and positive group were lower than those of low-dose group. The difference was statistically significant (P<0.05), while there was no significant difference between magnolidin high dose group and positive group (P>0.05). Conclusion: Magnolinin has significant effects on ARS, which may inhibit the inflammatory reaction of nasal mucosa through HMGB1/TLR4/NF-κB signaling pathway.
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