Arctigenin alleviates neuronal damage of acute cerebral infarction in rats by inhibiting the HMGB1/TLR4/NF-κB pathway

doi:10.11958/20221432

Abstract

Abstract:

Objective To explore whether arctigenin (AG) can reduce neuronal damage of acute cerebral infarction in rats by inhibiting the expression of high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. Methods The rat model of acute cerebral infarction was established by middle cerebral artery embolism (MCAO). Fifty model rats were randomly separated into the model group, the nimodipine group (30 mg/kg), the low AG group (25 mg/kg), the medium AG group (50 mg/kg) and the high AG group (100 mg/kg), 10 rats in each group. Another 10 rats were used as the sham operation group (only anesthesia, dissociation of blood vessel, no thrombus insertion operation). Morris water maze experiment was used to assess cognitive function in rats. The serum TNF-ɑ, IL-1β and IL-6 contents were tested by ELISA. HE staining and TUNEL staining were performed to observe the pathological changes and neuronal apoptosis of cerebral cortex, and Western blot assay was performed to measure the protein expression of HMGB1, TLR4, p-NF-κB and NF-κB. Results Compared with the sham operation group, the cognitive function was declined in the model group, serum levels of TNF-ɑ, IL-1β and IL-6 were increased, neuronal apoptosis index, cortical HMGB1 and TLR4 protein expression and p-NF-κB/NF-κB ratio were increased (P<0.05). The neuron arrangement of cerebral cortex was disordered, serious vacuolation, edema and nuclear condensation occurred. Compared with the model group, cognitive function was partially restored in the AG groups and the nimodipine group. Serum levels of TNF-ɑ, IL-1β and IL-6 decreased. Neuronal apoptosis index, cortical HMGB1, TLR4 protein expression and p-NF-κB/NF-κB ratio were decreased (P<0.05). Cortical neuron damage was reduced. (P<0.05). Conclusion AG may inhibit the HMGB1/TLR4/NF-κB pathway to reduce neuronal damage in rats with acute cerebral infarction.

Key words: high mobility group box 1, Toll-like receptor 4, nuclear factor κB, cerebral infarction, acute disease, neuron, Arctigenin

CLC Number:

R285.5

Figures/Tables 6

References 23

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组别	逃避潜伏期/s	原平台象限停留时间/s	进入原平台象限次数/次
假手术组	12.85±1.46	36.28±3.36	15.29±1.71
模型组	35.45±2.72^a	12.32±1.87^a	5.19±0.58^a
尼莫地平组	17.64±1.85^ab	28.51±2.52^ab	10.03±1.30^ab
AG低剂量组	26.85±2.29^abc	17.03±1.12^abc	6.92±0.62^abc
AG中剂量组	22.36±1.74^abcd	25.61±2.09^abcd	7.74±0.92^abcd
AG高剂量组	19.41±1.41^abde	29.91±2.16^abde	11.16±1.19^abde
F	161.760^＊＊	170.162^＊＊	102.376^＊＊

组别	逃避潜伏期/s	原平台象限停留时间/s	进入原平台象限次数/次
假手术组	12.85±1.46	36.28±3.36	15.29±1.71
模型组	35.45±2.72^a	12.32±1.87^a	5.19±0.58^a
尼莫地平组	17.64±1.85^ab	28.51±2.52^ab	10.03±1.30^ab
AG低剂量组	26.85±2.29^abc	17.03±1.12^abc	6.92±0.62^abc
AG中剂量组	22.36±1.74^abcd	25.61±2.09^abcd	7.74±0.92^abcd
AG高剂量组	19.41±1.41^abde	29.91±2.16^abde	11.16±1.19^abde
F	161.760^＊＊	170.162^＊＊	102.376^＊＊

组别	TNF-ɑ	IL-1β	IL-6
假手术组	36.33±3.11	16.23±1.66	23.21±2.11
模型组	119.57±11.75^a	96.85±7.38^a	116.89±13.34^a
尼莫地平组	45.72±5.22^ab	28.22±2.16^ab	39.21±3.16^ab
AG低剂量组	87.74±7.98^abc	65.21±6.35^abc	80.24±6.11^abc
AG中剂量组	65.88±5.67^abcd	46.55±4.56^abcd	66.71±5.39^abcd
AG高剂量组	48.46±3.19^abde	28.76±3.12^abde	40.24±3.89^abde
F	210.617^＊＊	402.212^＊＊	258.861^＊＊

组别	TNF-ɑ	IL-1β	IL-6
假手术组	36.33±3.11	16.23±1.66	23.21±2.11
模型组	119.57±11.75^a	96.85±7.38^a	116.89±13.34^a
尼莫地平组	45.72±5.22^ab	28.22±2.16^ab	39.21±3.16^ab
AG低剂量组	87.74±7.98^abc	65.21±6.35^abc	80.24±6.11^abc
AG中剂量组	65.88±5.67^abcd	46.55±4.56^abcd	66.71±5.39^abcd
AG高剂量组	48.46±3.19^abde	28.76±3.12^abde	40.24±3.89^abde
F	210.617^＊＊	402.212^＊＊	258.861^＊＊

组别	HMGB1/β-actin	TLR4/β-actin	p-NF-κB/NF-κB
假手术组	0.11±0.01	0.16±0.02	0.09±0.01
模型组	0.69±0.07^a	1.21±0.11^a	0.53±0.05^a
尼莫地平组	0.24±0.02^ab	0.33±0.02^ab	0.16±0.02^ab
AG低剂量组	0.52±0.04^abc	0.97±0.10^abc	0.36±0.04^abc
AG中剂量组	0.38±0.03^abcd	0.65±0.07^abcd	0.28±0.02^abcd
AG高剂量组	0.26±0.03^abde	0.36±0.04^abde	0.17±0.01^abde
F	151.045^＊＊	170.313^＊＊	153.118^＊＊