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

作　　者：张瑞芹 胡云磊 王芳 闫保星[2] Zhang Ruiqin;Hu Yunlei;Wang Fang;Yan Baoxing(Xinyang Central Hospital,Xinyang 464000,China;Zhengzhou Second Hospital,Zhengzhou 450015,China)

机构地区：[1]信阳市中心医院,信阳464000 [2]郑州市第二人民医院,郑州450015

出　　处：《中国药事》2022年第5期526-534,共9页Chinese Pharmaceutical Affairs

基　　金：河南省医学科技攻关计划项目(编号LHGJ20191016)。

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�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

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 

分 类 号：R961.1[医药卫生—药理学]