Effect and mechanism of tetrandrine on airway remodeling in bronchial asthma mice

doi:10.11958/20222063

Abstract

Abstract:

Objective To investigate the effect of tetrandrine on airway remodeling and high mobility group protein box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in bronchial asthma mice. Methods A mouse model of bronchial asthma was established, and 40 model mice were randomly divided into the model group, the tetrandrine low dose (20 mg/kg) group, the high dose (40 mg/kg) group and the dexamethasone (10 mg/kg) group, with 10 mice in each group. Another 10 mice without modeling were useed as the control group. Each group was given corresponding intervention for 2 weeks. Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL-6) and IL-1β were determined by ELISA. Hematoxylin-eosin staining was used to observe lung histopathological changes, and lung injury score was performed. The thickness of bronchial tube wall and bronchial smooth muscle were determined. Expression levels of HMGB1, TLR4, NF-κB mRNA and protein in lung tissue were detected by fluorescence quantitative PCR (qPCR) and Western blot assay. Results No pathological damage was found in bronchus of lung tissue in the control group. Compared with the control group, the bronchial tube wall and smooth muscle of lung tissue in the model group were thickened, mucosal epithelium hyperplasia, and lumen shrank and tracheal mucus exudated significantly. Serum levels of TNF-α, IL-6 and IL-1β, lung injury score, bronchial wall thickness, bronchial smooth muscle thickness, HMGB1, TLR4, NF-κB mRNA and protein expression levels were increased significantly (P<0.05). Compared with the model group, the degree of lung lesions was gradually reduced in the low and high dose tetrandrine groups, and serum levels of TNF-α, IL-6, IL-1β, lung injury scores, bronchial wall and bronchial smooth muscle thickness, HMGB1, TLR4, NF-κB mRNA and protein expression were successively decreased. There were no significant differences in above indexed between the tetrandrine high dose group and the dexamethasone group (P>0.05). Conclusion Tetrandrine can reduce the degree of airway remodeling and the level of inflammatory factors in mice with bronchial asthma, and protect lung tissue, which may be related to the inhibition of HMGB1/TLR4/NF-κB signal pathway.

Key words: tetrandrine, asthma, airway remodeling, HMGB1 protein, Toll-like receptor 4, NF-kappa B

CLC Number:

R562.25，R349.6

Figures/Tables 7

References 21

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基因名称	引物序列（5′→3′）	产物大小/bp
HMGB1	上游：AGGATGCTTCTGTCAACT	198
	下游：TCAGCTTGGCAGCTTTTC	198
TLR4	上游：GGTGAGAAATGAGCTGGTA	559
	下游：TCTGCTAAGAAGGCGATAT	559
NF-κB	上游：ACAGCACAGATACCACTAAG	159
	下游：CTGCCTCATAGAAGCCATCC	159
GAPDH	上游：CCACTTGAAGGGTGGAGC	112
	下游：TGTAGTCGCAGGACACAA	112

基因名称	引物序列（5′→3′）	产物大小/bp
HMGB1	上游：AGGATGCTTCTGTCAACT	198
	下游：TCAGCTTGGCAGCTTTTC	198
TLR4	上游：GGTGAGAAATGAGCTGGTA	559
	下游：TCTGCTAAGAAGGCGATAT	559
NF-κB	上游：ACAGCACAGATACCACTAAG	159
	下游：CTGCCTCATAGAAGCCATCC	159
GAPDH	上游：CCACTTGAAGGGTGGAGC	112
	下游：TGTAGTCGCAGGACACAA	112

组别	TNF-α	IL-6	IL-1β
对照组	45.12±3.05	34.92±3.95	23.57±1.79
模型组	106.08±9.13^a	79.38±8.15^a	85.73±6.03^a
汉防己甲素低剂量组	84.58±7.07^b	66.02±5.11^b	70.14±5.88^b
汉防己甲素高剂量组	70.24±5.11^bc	49.85±4.04^bc	56.52±4.86^bc
地塞米松组	68.93±5.14^bc	51.66±4.02^bc	55.83±4.91^bc
F	128.734^＊＊	101.994^＊＊	216.221^＊＊

组别	TNF-α	IL-6	IL-1β
对照组	45.12±3.05	34.92±3.95	23.57±1.79
模型组	106.08±9.13^a	79.38±8.15^a	85.73±6.03^a
汉防己甲素低剂量组	84.58±7.07^b	66.02±5.11^b	70.14±5.88^b
汉防己甲素高剂量组	70.24±5.11^bc	49.85±4.04^bc	56.52±4.86^bc
地塞米松组	68.93±5.14^bc	51.66±4.02^bc	55.83±4.91^bc
F	128.734^＊＊	101.994^＊＊	216.221^＊＊

组别	支气管管壁厚度	支气管平滑肌厚度
对照组	37.52±1.55	12.81±0.24
模型组	63.85±4.67^a	22.04±0.76^a
汉防己甲素低剂量组	53.07±4.59^b	18.25±0.68^b
汉防己甲素高剂量组	45.56±3.57^bc	15.16±0.41^bc
地塞米松组	46.82±3.52^bc	14.72±0.42^bc
F	68.310^＊＊	453.229^＊＊