Effect and mechanism of sodium ferulate on Ménière disease model mice

doi:10.11958/20231044

Abstract

Abstract:

Objective To investigate the effect and mechanism of sodium ferulate in the treatment of Ménière disease (MD) model mice. Methods BALB/c mice were selected, and an MD model was constructed using posterior fossa epidural approach combined with intraperitoneal injection of aldosterone. Sixty model mice were randomly grouped into the model group, the low dose sodium ferulate group, the medium dose sodium ferulate group, the high dose sodium ferulate group and the dexamethasone group, with 12 mice in each group. Another 12 BALB/c mice were selected as the sham operation group. After grouping and tympanic administration, auditory evoked brainstem response (ABR) was applied to detect the hearing level of mice in each group. HE staining and magnetic resonance imaging (MRI) were applied to observe the morphology of cochlea and membranous labyrinth hydrops of mice in each group. Enzyme-linked immunosorbent assay was applied to detect serum levels of lipoprotein a [Lp(a)], pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in each group. Immunohistochemical staining and Western blot assay were applied to detect the expression of Lp(a) in each group. Results Compared with the sham operation group, the ABR threshold, the score of membranous labyrinth hydrops, the proportion of middle stage area, serum levels of Lp(a), IL-6 and TNF-α, the IOD value of Lp(a) positive expression and the expression of Lp(a) protein in the cochlea of mice were significantly increased in the model group (P<0.05). Compared with the model group, the ABR threshold, the score of membranous labyrinth hydrops, the proportion of middle stage area, levels of serum Lp(a), IL-6 and TNF-α, the IOD value of Lp(a) positive expression and the expression of Lp(a) protein in the cochlea of mice were significantly decreased in the low, medium and high dose sodium ferulate groups and the dexamethasone group (P<0.05), and the effect of high dose sodium ferulate was more obvious. Conclusion Sodium ferulate can down regulate the expression of Lp(a) protein, reduce the production of proinflammatory factors, inhibit the inflammatory reaction, thereby alleviating the symptoms of membranous labyrinth hydrops in MD mice, and improving their auditory function.

Key words: Ménière disease, lipoprotein(a), sodium ferulate, tympanic administration

CLC Number:

R764.3

Figures/Tables 7

References 20

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组别	ABR阈值/ dB nHL	膜迷路积水评分/分	中阶面积占比/%
假手术组	21.13±2.30	0.00±0.00	24.87±4.36
模型组	59.62±5.06^a	3.50±0.45^a	70.45±6.23^a
阿魏酸钠低剂量组	47.71±3.84^b	2.33±0.35^b	56.18±3.81^b
阿魏酸钠中剂量组	35.40±2.43^bc	1.50±0.20^bc	42.36±3.45^bc
阿魏酸钠高剂量组	23.75±2.75^bcd	0.67±0.15^bcd	28.12±3.79^bcd
地塞米松组	23.24±2.25^bcd	0.50±0.10^bcd	27.05±3.26^bcd
F	274.900^＊＊	311.000^＊＊	226.600^＊＊

组别	ABR阈值/ dB nHL	膜迷路积水评分/分	中阶面积占比/%
假手术组	21.13±2.30	0.00±0.00	24.87±4.36
模型组	59.62±5.06^a	3.50±0.45^a	70.45±6.23^a
阿魏酸钠低剂量组	47.71±3.84^b	2.33±0.35^b	56.18±3.81^b
阿魏酸钠中剂量组	35.40±2.43^bc	1.50±0.20^bc	42.36±3.45^bc
阿魏酸钠高剂量组	23.75±2.75^bcd	0.67±0.15^bcd	28.12±3.79^bcd
地塞米松组	23.24±2.25^bcd	0.50±0.10^bcd	27.05±3.26^bcd
F	274.900^＊＊	311.000^＊＊	226.600^＊＊

组别	Lp（a）/（μg/L）	IL-6/（ng/L）	TNF-α/（ng/L）
假手术组	82.74±17.32	142.15±19.32	172.85±22.35
模型组	251.26±33.54^a	418.64±45.36^a	834.20±71.54^a
阿魏酸钠低剂量组	197.12±21.26^b	327.96±32.25^b	613.42±58.20^b
阿魏酸钠中剂量组	145.20±20.64^bc	239.41±22.52^bc	397.85±42.64^bc
阿魏酸钠高剂量组	93.06±18.42^bcd	153.02±20.45^bcd	183.62±30.42^bcd
地塞米松组	89.75±16.85^bcd	148.56±18.68^bcd	176.36±26.16^bcd
F	116.200^＊＊	197.700^＊＊	443.000^＊＊

组别	Lp（a）/（μg/L）	IL-6/（ng/L）	TNF-α/（ng/L）
假手术组	82.74±17.32	142.15±19.32	172.85±22.35
模型组	251.26±33.54^a	418.64±45.36^a	834.20±71.54^a
阿魏酸钠低剂量组	197.12±21.26^b	327.96±32.25^b	613.42±58.20^b
阿魏酸钠中剂量组	145.20±20.64^bc	239.41±22.52^bc	397.85±42.64^bc
阿魏酸钠高剂量组	93.06±18.42^bcd	153.02±20.45^bcd	183.62±30.42^bcd
地塞米松组	89.75±16.85^bcd	148.56±18.68^bcd	176.36±26.16^bcd
F	116.200^＊＊	197.700^＊＊	443.000^＊＊

组别	IOD值	Lp（a）/GAPDH
假手术组	5.31±0.64	0.15±0.04
模型组	16.24±3.31^a	1.18±0.15^a
阿魏酸钠低剂量组	12.97±2.40^b	0.83±0.09^b
阿魏酸钠中剂量组	9.46±1.51^bc	0.50±0.06^bc
阿魏酸钠高剂量组	6.02±0.59^bcd	0.29±0.04^bcd
地塞米松组	5.76±0.70^bcd	0.27±0.03^bcd
F	71.750^＊＊	299.800^＊＊