The effect of securinine on neurological function recovery after cerebral ischemia-reperfusion injury in rats

doi:10.11958/20221801

Abstract

Abstract:

Objective To explore the effect and mechanism of securinine (SE) on cerebral ischemia reperfusion injury (CIRI) in rats based on toll-like receptor 4 (TLR4)/nuclear transcription factor-kappa B (NF-κB) pathway. Methods A total of 100 male or female adult SD rats were randomly divided into the sham group, the CIRI group and the SE low-, medium- and high-dose (20 mg/kg, 40 mg/kg, 80 mg/kg) groups, with 20 rats in each group. The rat model of CIRI was established by thread occlusion. Rats were treated with SE (20 mg/kg, 40 mg/kg and 80 mg/kg) immediately after successful modeling for 3 consecutive days. Rats in the sham group and the CIRI group were given the same amount of normal saline. At 24 h, 48 h and 72 h after operation, the neurological deficits of rats were measured according to Longa score. At 72 h after operation, brain tissue water content was evaluated by wet-dry weight method, and the percentage of cerebral infarction volume was assessed by triphenyltetrazolium chloride (TTC) staining. Protein expression levels of Iba-1，TLR4, NF-κB p65 and p-NF-κB p65 in brain tissue were determined by Western blot assay. Expression levels of inflammatory factors such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Level of microglia activation and the number of surviving neurons were examined by immunofluorescence staining. Results Compared with the sham group, neurological function scores, brain tissue water content and the percentage of cerebral infarction volume were significantly increased in the CIRI group (all P<0.05). Expression levels of TLR4, p-NF-κB p65, Iba-1, IL-1β, TNF-α and IL-6 in brain tissue were significantly increased (all P<0.05). However, medium- and high-doses of SE could significantly alleviate the neurological deficits, reduce the water content of brain tissue and the size of cerebral infarction volume, decrease expression levels of TLR4, p-NF-κB p65, Iba-1, IL-1β, TNF-α and IL-6 in the injured area of brain tissue in rats. Conclusion SE can alleviate CIRI-induced neuroinflammatory response via inhibiting TLR4/NF-κB pathway activation, thereby conferring a protective role in brain of rats.

Key words: brain ischemia, reperfusion injury, TLR4/NF-κB pathway, securinine, inflammatory factors

CLC Number:

R743.3

Figures/Tables 8

References 21

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组别	n	神经功能缺损评分/分
组别	n	24 h	48 h	72 h
Sham组	8	0.00±0.00	0.00±0.00	0.00±0.00
CIRI组	8	2.75±0.39^a	2.70±0.38^a	2.46±0.40^a
SE低剂量组	8	2.71±0.38	2.46±0.43	2.33±0.44
SE中剂量组	8	2.42±0.35	2.25±0.43^b	1.95±0.38^bc
SE高剂量组	8	2.21±0.40^b	1.83±0.44^b	1.33±0.40^bcd
F		3.687^＊	6.249^＊	12.625^＊

组别	n	神经功能缺损评分/分
组别	n	24 h	48 h	72 h
Sham组	8	0.00±0.00	0.00±0.00	0.00±0.00
CIRI组	8	2.75±0.39^a	2.70±0.38^a	2.46±0.40^a
SE低剂量组	8	2.71±0.38	2.46±0.43	2.33±0.44
SE中剂量组	8	2.42±0.35	2.25±0.43^b	1.95±0.38^bc
SE高剂量组	8	2.21±0.40^b	1.83±0.44^b	1.33±0.40^bcd
F		3.687^＊	6.249^＊	12.625^＊

组别	n	脑梗死体积百分比	n	脑组织含水量
Sham组	5	0.00±0.00	6	66.54±2.37
CIRI组	5	42.53±3.00^a	6	82.49±7.30^a
SE低剂量组	5	39.18±3.27	6	79.18±7.76
SE中剂量组	5	27.02±2.45^bc	6	73.17±8.63^b
SE高剂量组	5	16.91±2.17^bcd	6	68.78±8.33^bc
F		90.629^＊		5.204^＊

组别	n	脑梗死体积百分比	n	脑组织含水量
Sham组	5	0.00±0.00	6	66.54±2.37
CIRI组	5	42.53±3.00^a	6	82.49±7.30^a
SE低剂量组	5	39.18±3.27	6	79.18±7.76
SE中剂量组	5	27.02±2.45^bc	6	73.17±8.63^b
SE高剂量组	5	16.91±2.17^bcd	6	68.78±8.33^bc
F		90.629^＊		5.204^＊

组别	TLR4/ β-actin	p-NF-κB p65/ t-NF-κB p65	p-NF-κB/ β-actin	Iba-1/ β-actin
Sham组	0.36±0.03	0.66±0.05	0.45±0.05	0.29±0.05
CIRI组	0.57±0.04^a	1.19±0.06^a	0.86±0.07^a	0.76±0.06^a
SE低剂量组	0.55±0.04	1.08±0.07	0.76±0.07	0.68±0.06
SE中剂量组	0.40±0.04^bc	0.73±0.05^bc	0.49±0.05^bc	0.39±0.06^bc
SE高剂量组	0.39±0.04^bc	0.67±0.06^bc	0.47±0.05^bc	0.29±0.05^bcd
F	45.248^＊	101.488^＊	61.862^＊	92.760^＊