Effect of oxymatrine on cerebral vasospasm in subarachnoid hemorrhage rats and its related mechanism

doi:10.3877/cma.j.issn.1674-6880.2016.05.007

Abstract

Abstract:

Objective

To investigate the effect of oxymatrine (OMT) on cerebral vasospasm in rats with subarachnoid hemorrhage (SAH) and its related mechanism.

Methods

Two hundred rats were randomly divided into the sham group, SAH group, low and high dose treatment groups with 50 rats in each group. The SAH rat model was established by two injections of the autogenous blood into the cisterna magna, and rats in the sham group were only injected with the same volume saline twice. After surgery, the other three groups were given an intraperitoneal injection of 1 ml 0.9% sodium chloride, 60 or 120 mg/kg OMT, respectively. Ten rats from each group were sacrificed at 1, 3, 5, 7 and 10 d. The diameter of basilar artery was measured and the expression levels of nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) mRNA in endothelial cells were detected.

Results

At day 3, 5, 7 and 10 after surgery, the significant differences were found in the diameter of basilar artery (F = 11.897, 28.957, 14.785, 8.381; all P < 0.05), as well as the protein expression levels of NF-κB (F = 17.289, 65.602, 43.881, 26.998; all P < 0.05), ERK1/2 (F = 204.331, 145.948, 107.442, 30.332; all P < 0.05), p38 MAPK (F = 84.908, 116.677, 83.735, 28.338; all P < 0.05), JNK (F = 26.809, 83.419, 56.465, 27.756; all P < 0.05), and the mRNA expression levels of IL-1β(F = 66.625, 262.620, 283.499, 218.081; all P < 0.05), IL-6 (F = 38.580, 170.657, 136.253, 58.068; all P < 0.05) and TNF-α (F = 31.290, 361.661, 101.109, 23.940; all P < 0.05) among all four groups. Compared with the SAH group, at 3, 5, 7 and 10 d, the diameter of basilar artery in the sham and high dose treatment groups were dilated obviously (all P < 0.05), as well as protein expression levels of NF-κB, ERK1/2, p38 MAPK, JNK and mRNA expression levels of IL-1β, IL-6 and TNF-α were significantly decreased (all P < 0.05). However, these effects in the low dose treatment group were not obvious (all P > 0.05).

Conclusions

OMT could inhibit cerebral vasospasm of rats with SAH. It may reduce vascular inflammatory reaction of basilar artery via OMT-depressed NF-κB, ERK1/2, p38MAPK and JNK signaling pathways in cerebrovascular endothelial cells.

Key words: Subarachnoid hemorrhage, Vasospasm, Intracranial, Rats, Oxymatrine, Inflammatory response

Xianqiang Wen, Weimin Dai, Qiang Huang, Guofeng Yu, Xinjiang Yan. Effect of oxymatrine on cerebral vasospasm in subarachnoid hemorrhage rats and its related mechanism[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2016, 09(05): 321-327.

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Figures/Tables 8

References 21

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组别	只数	术后不同时间点基底动脉直径
组别	只数	1d	3d	5d	7d	10 d
假手术组	10	225 ± 13	224 ± 12^a	225 ± 10^a	224 ± 13^a	223 ± 13^a
SAH组	10	218 ± 12	186 ± 8	169 ± 7	180 ± 8	189 ± 8
小剂量组	10	220 ± 12	191 ± 11	172 ± 12	185 ± 12	192 ± 14
大剂量组	10	223 ± 11	207 ± 13^a	188 ± 13^a	201 ± 12^a	210 ± 12^a
F值	?	0.393	11.897	28.957	14.785	8.381
P值	?	0.760	<0.001	<0.001	<0.001	0.001

组别	只数	术后不同时间点基底动脉直径
组别	只数	1d	3d	5d	7d	10 d
假手术组	10	225 ± 13	224 ± 12^a	225 ± 10^a	224 ± 13^a	223 ± 13^a
SAH组	10	218 ± 12	186 ± 8	169 ± 7	180 ± 8	189 ± 8
小剂量组	10	220 ± 12	191 ± 11	172 ± 12	185 ± 12	192 ± 14
大剂量组	10	223 ± 11	207 ± 13^a	188 ± 13^a	201 ± 12^a	210 ± 12^a
F值	?	0.393	11.897	28.957	14.785	8.381
P值	?	0.760	<0.001	<0.001	<0.001	0.001

组别	只数	术后不同时间点NF-κB蛋白相对表达量
组别	只数	1d	3d	5d	7d	10 d
假手术组	10	1.00 ± 0.07	1.09 ± 0.15^a	1.03 ± 0.05^a	1.09 ± 0.17^a	1.06 ± 0.14^a
SAH组	10	1.11 ± 0.16	2.03 ± 0.26	3.41 ± 0.33	2.76 ± 0.25	2.22 ± 0.30
小剂量组	10	1.09 ± 0.12	1.93 ± 0.26	3.27 ± 0.37	2.54 ± 0.35	2.12 ± 0.28
大剂量组	10	1.07 ± 0.14	1.54 ± 0.23^a	2.30 ± 0.28^a	1.89 ± 0.22^a	1.46 ± 0.21^a
F值	?	0.758	17.289	65.602	43.881	26.998
P值	?	0.534	<0.001	<0.001	<0.001	0.001

组别	只数	术后不同时间点NF-κB蛋白相对表达量
组别	只数	1d	3d	5d	7d	10 d
假手术组	10	1.00 ± 0.07	1.09 ± 0.15^a	1.03 ± 0.05^a	1.09 ± 0.17^a	1.06 ± 0.14^a
SAH组	10	1.11 ± 0.16	2.03 ± 0.26	3.41 ± 0.33	2.76 ± 0.25	2.22 ± 0.30
小剂量组	10	1.09 ± 0.12	1.93 ± 0.26	3.27 ± 0.37	2.54 ± 0.35	2.12 ± 0.28
大剂量组	10	1.07 ± 0.14	1.54 ± 0.23^a	2.30 ± 0.28^a	1.89 ± 0.22^a	1.46 ± 0.21^a
F值	?	0.758	17.289	65.602	43.881	26.998
P值	?	0.534	<0.001	<0.001	<0.001	0.001

组别	只数	术后不同时间点ERK1/2蛋白相对表达量
组别	只数	1d	3d	5d	7d	10 d
假手术组	10	1.00 ± 0.08	1.07 ± 0.08^a	1.05 ± 0.06^a	0.99 ± 0.07^a	1.00 ± 0.06^a
SAH组	10	1.23 ± 0.27	2.60 ± 0.14	5.31 ± 0.48	3.10 ± 0.21	2.07 ± 2.26
小剂量组	10	1.20 ± 0.21	2.49 ± 0.16	5.00 ± 0.40	2.90 ± 0.30	2.00 ± 0.22
大剂量组	10	1.17 ± 0.11	1.84 ± 0.14^a	3.60 ± 0.35^a	2.08 ± 0.17^a	1.57 ± 0.20^a
F值	?	1.553	204.331	145.948	107.442	30.332
P值	?	0.240	<0.001	<0.001	<0.001	0.001

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