文献类型：期刊文献

中文题名：基于TLR4/MyD88/NF-κB信号通路探讨龙牡安神颗粒对慢性束缚应激小鼠焦虑行为的影响

英文题名：Effects of Longmu Anshen Granules on anxiety-like behavior in mice exposed to chronic restraint stress based on research of TLR4/MyD88/NF-κB signaling pathway

作者：赵建军[1];彭晓明[1,2];李婷婷[1];朱鑫磊[1];王伟龙[1];漆哲宁[1];刘立[1]

第一作者：赵建军

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2022

卷号：44

期号：11

起止页码：3476

中文期刊名：中成药

外文期刊名：Chinese Traditional Patent Medicine

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：甘肃省自然科学基金项目(20JR10RA338);2022年甘肃中医药大学研究生创新创业基金项目(2022CX42)。

语种：中文

中文关键词：龙牡安神颗粒;慢性束缚应激;焦虑;TLR4/MyD88/NF-κB信号通路;炎症因子

外文关键词：Longmu Anshen Granules;chronic restraint stress;anxiety;TLR4/MyD88/NF-κB signaling pathway;inflammatory factor

摘要：目的基于TLR4/MyD88/NF-κB信号通路探讨龙牡安神颗粒对慢性束缚应激小鼠焦虑行为的影响。方法将48只小鼠随机分为空白组、模型组、盐酸帕罗西汀组(2.6 mg/kg)及龙牡安神颗粒高、中、低剂量组(4.16、2.08、1.04 g/kg),除空白组外,其余各组小鼠采用慢性束缚应激复制焦虑模型,连续束缚35 d。从第15天开始,每天束缚结束后0.5 h,空白组和模型组灌胃给予蒸馏水,给药组灌胃给予相应药物,连续21 d。通过高架十字迷宫实验和旷场实验观察小鼠行为学的变化,酶联免疫吸附测定法(ELISA)检测海马组织匀浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6水平,RT-qPCR和Western blot法分别检测海马组织中TLR4、MyD88、NF-κB mRNA及蛋白表达,免疫组化法检测海马组织中磷酸化NF-κB(p-NF-κB)蛋白表达。结果与空白组比较,模型组小鼠对高架十字迷宫开臂和旷场实验中央区域的探索行为减少(P<0.01),海马组织中TLR4、MyD88、NF-κB mRNA及蛋白表达、p-NF-κB蛋白表达及TNF-α、IL-1β、IL-6水平均升高(P<0.01);与模型组比较,龙牡安神颗粒高、中剂量组均可改善上述指标(P<0.05,P<0.01)。结论龙牡安神颗粒能改善慢性束缚应激小鼠的焦虑行为,其机制可能与抑制TRL4/MyD88/NF-κB信号通路,减少促炎介质的释放和表达有关。
AIM To investigate the effects of Longmu Anshen Granules on anxiety-like behavior in mice exposed to chronic restraint stress based on research of TLR4/MyD88/NF-κB signaling pathway.METHODS Forty-eight mice were randomly divided into the blank group,the model group,paroxetine hydrochloride group(2.6 mg/kg),and Longmu Anshen Granules groups(high dose of 4.16 g/kg,medium dose of 2.08 g/kg,low dose of 1.04 g/kg).Mice of all the groups,except the blank group,were exposed to repeated restraint stress continuously for 35 days to replicate anxiety models.Ever since 0.5 h after the end of daily restraint on the 15th day,gavage of distilled water in the blank group and the model group,and gavage of the corresponding drugs in the other administration groups went on for 21 days.The mice were subjected to the assessment of anxiety behavior by elevated plus maze and open field test;the determination of their levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 by enzyme-linked immunosorbent assay(ELISA);the detection of the mRNA and protein expressions of TLR4,MyD88 and NF-κB in hippocampal tissue by RT-qPCR and Western blot,respectively;and the detection of the expression of phosphorylated NF-κB(p-NF-κB)in hippocampal tissue by immunohistochemistry.RESULTS Compared with the blank group,the model group displayed decreased exploratory behavior in the open arm of elevated plus maze and the central area of open field test(P<0.01),and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB,expression of p-NF-κB protein and levels of TNF-α,IL-1βand IL-6 in the hippocampus(P<0.01).Compared with the model group,the groups intervened with high dose and medium dose Longmu Anshen Granules performed much better in terms of the aforementioned indicators levels(P<0.05,P<0.01).CONCLUSION Longmu Anshen Granules can ameliorate the anxiety-like behavior of mice exposed to chronic restraint stress,and its mechanism may be related to the inhibition of TRL4/MyD88/NF-κB signaling pathway and reduction of the release and expression of pro-inflammatory mediators.