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1.浙江中医药大学 基础医学院,杭州 310053
2.浙江中医药大学 附属第一医院,杭州 310006
*龚婉,硕士,助理实验师,从事中药药效物质基础研究,E-mail: gongw@zcmu.edu.cn
收稿日期:2018-09-06,
网络出版日期:2018-11-16,
纸质出版日期:2019-02-05
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龚婉, 陈晓玲, 周莉, 等. 阿魏酸钠对大鼠脑缺血再灌注炎症损伤的保护作用及机制分析[J]. 中国实验方剂学杂志, 2019,25(3):94-99.
Wan GONG, Xiao-ling CHEN, Li ZHOU, et al. Protective Effect and Mechanism of Sodium Ferulate on Cerebral Ischemia-reperfusion Inflammatory Injury in Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(3): 94-99.
龚婉, 陈晓玲, 周莉, 等. 阿魏酸钠对大鼠脑缺血再灌注炎症损伤的保护作用及机制分析[J]. 中国实验方剂学杂志, 2019,25(3):94-99. DOI: 10.13422/j.cnki.syfjx.20190341.
Wan GONG, Xiao-ling CHEN, Li ZHOU, et al. Protective Effect and Mechanism of Sodium Ferulate on Cerebral Ischemia-reperfusion Inflammatory Injury in Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(3): 94-99. DOI: 10.13422/j.cnki.syfjx.20190341.
目的:
2
观察阿魏酸钠对大鼠脑缺血再灌注炎症损伤的保护作用,并探讨其作用机制。
方法:
2
取SD雄性大鼠,建立大脑中动脉阻塞(MCAO)致脑缺血/再灌注损伤模型,造模成功的36只随机分成模型组,阿魏酸钠低、中、高剂量组(25,50,100 mg·kg
-1
),并另取9只作为假手术组。采用神经功能评分法观察大鼠神经功能情况;苏木精-伊红(HE)染色观察大鼠脑组织病理学形态变化;酶联免疫吸附测定(ELISA)检测大鼠血清和脑组织中肿瘤坏死因子-
α
(TNF-
α
),白细胞介素-1
β
(IL-1
β
),白细胞介素-6(IL-6)含量变化;蛋白免疫印迹法(Western blot)检测缺血周边区核转录因子-кB p65(NF-
κ
B p65)蛋白表达。
结果:
2
与假手术组比较,模型组大鼠神经行为学评分升高,神经元坏死,大量炎症细胞产生,血清和脑组织中TNF-
a
,IL-1
β
,IL-6水平显著升高(
P
<
0.01),细胞核/细胞浆NF-
κ
B p65蛋白表达比例显著升高(
P
<
0.01);与模型组比较,阿魏酸钠可明显降低脑损伤大鼠神经行为学评分(
P
<
0.05,
P
<
0.01),抑制神经元坏死,减少炎症细胞产生,并可明显降低血清和脑组织中TNF-
a
,IL-1
β
,IL-6水平(
P
<
0.05,
P
<
0.01),抑制NF-
κ
B p65由细胞质向细胞核转位(
P
<
0.05,
P
<
0.01),最终减轻缺血再灌注造成的神经细胞炎症损伤。
结论:
2
阿魏酸钠可通过抑制NF-
κ
B p65核转位减轻缺血再灌注大鼠脑神经细胞炎症反应,维持脑部正常形态,这可能是其发挥脑保护作用的机制之一。
Objective:
2
To investigate the protective effect of sodium ferulate on cerebral ischemia-reperfusion injury in rats and to explore its possible mechanism.
Method:
2
The cerebral ischemia reperfusion injury model was established by middle cerebral artery occlusion (MCAO) in SD male rats. 36 modeled rats with neurologic damage were randomly divided into 4 groups: model group
low
medium
high-dose sodium ferulate groups (25
50
100 mg·kg
-1
). Another nine rats were selected as a sham operation group.Neurological function was assessed by neurological scoring system in rats.Hematoxylin-eosin (HE) staining was performed to observe the pathological changes of the rats' brain. The levels of tumor necrosis factor
α
(TNF-
α
)
interleukin-1
β
(IL-1
β
) and interleukin-6 (IL-6) in serum and brain tissues were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein expression of nucleus and cytoplasm nuclear factor-kappa B p65 (NF-
κ
B p65) in brain tissues.
Result:
2
As compared with normal group
neurological deficit score was increased; the neuronal necrosis and inflammatory cell number were present; the serum and brain tissue levels of TNF-
α
IL-1
β
and IL-6 were increased; nucleus/cytoplasm NF-
κ
B p65 protein expression ratio was increased significantly in model group (
P
<
0.01). As compared with model group
sodium ferulate distinctly decreased the neurological deficit score(
P
<
0.05
P
<
0.01)
inhibited neuronal necrosis
reduce inflammatory cell number
significantly reduce the serum and brain tissue levels of TNF-
α
IL-1
β
and IL-6(
P
<
0.05
P
<
0.01). Western blot showed that sodium ferulate could inhibit the nuclear translocation of NF-
κ
B p65 protein(
P
<
0.05
P
<
0.01)
and finally
it can alleviate the inflammatory injury caused by ischemia reperfusion.
Conclusion:
2
Sodium ferulate protects the brain against focal cerebral ischemia reperfusion injury
and the mechanism may be related to inhibiting nuclear translocation of NF-
κ
B p65 protein to alleviate inflammatory response.
陈丹丹 , 彭成 , 万峰 , 等 . 氢溴酸樟柳碱对抗大鼠急性脑缺血/再灌注损伤的作用机制研究 [J]. 中国药理学通报 , 2017 , 33 ( 8 ): 1096 - 1102 .
丁素菊 , 吴雄枫 . 脑卒中诊断治疗指南的缺陷——点评《中国急性缺血性脑卒中诊治指南2014》 [J]. 医学与哲学(B) , 2016 , 37 ( 6 ): 13 - 16 .
CHEN Y K , ZHANG L , NI J S , et al . Lldt-8 protects against cerebral ischemia/reperfusion injury by suppressing post-stroke inflammation [J]. J Pharmacol Sci , 2016 , 131 ( 2 ): 131 - 137 .
于凌志 , 左艳丽 , 贾孟辉 , 等 . 核转录因子NF- κ B对脑缺血再灌注干预机制的研究进展 [J]. 中国民族医药杂志 , 2015 , 21 ( 7 ): 42 - 44 .
秦文熠 , 荣晓凤 , 陶涛 , 等 . 核转录因子- κ B拮抗剂对大鼠海马CA1区局灶性脑缺血再灌注损伤的影响 [J]. 中华神经科杂志 , 2016 , 49 ( 1 ): 45 - 53 .
Ou S , Kwok K C. Ferulic acid: pharmaceutical functions, preparation and applications in foods [J]. J Sci Food Agric , 2004 , 84 ( 11 ): 1261 - 1269 .
管咏梅 , 陶玲 , 朱小芳 , 等 . 乳香没药挥发油对川芎中阿魏酸促透机制的研究 [J]. 中国中药杂志 , 2017 , 42 ( 17 ): 3350 - 3355 .
Mancuso C , Santangelo R. Ferulic acid: pharmacological and toxicological aspects [J]. Food Chem Toxicol , 2014 , 65 ( 2 ): 185 - 195 .
REN Z K , ZHANG R P , LI Y Y , et al . Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo [J]. Int J Mol Med , 2017 , 40 ( 5 ): 1444 - 1456 .
Koh P O . Ferulic acid attenuates the down-regulation of mek/erk/p90rsk signaling pathway in focal cerebral ischemic injury [J]. Neurosci Lett , 2015 , 588 : 18 - 23 .
ZHANG Q , ZHAO Y H , XU Y H , et al . Sodium ferulate and n-butylidenephthalate combined with bone marrow stromal cells (BMSCs) improve the therapeutic effects of angiogenesis and neurogenesis after rat focal cerebral ischemia [J]. J Transl Med , 2016 , 14 ( 1 ): 223 - 238 .
Sasaki M , Honmou O , Kocsis J D. A rat middle cerebral artery occlusion model and intravenous cellular delivery [J]. Methods Mol Biol , 2009 , 549 : 187 - 195 .
Longa E Z , Weinstein P R , Carlson S , et al . Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke , 1989 , 20 ( 1 ): 84 - 91 .
李子广 , 吴华璞 , 郭梅 , 等 . 阿魏酸钠对MCAO大鼠缺血/再灌注损伤p38MAPK信号通路的影响 [J]. 中西医结合心脑血管病杂志 , 2009 , 7 ( 2 ): 193 - 195 .
TANG Q Q , HAN R D , XIAO H , et al . Protective effect of tanshinone IIA on the brain and its therapeutic time window in rat models of cerebral ischemia-reperfusion [J]. Exp Ther Med , 2014 , 8 ( 5 ): 1616 - 1622 .
刘抒雯 , 杨丽华 , 马春 , 等 . 中医药保护脑缺血再灌注损伤后神经血管单元的作用 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 21 ): 225 - 234 .
Danton G H , Dietrich W D. Inflammatory mechanisms after ischemia and stroke [J]. J Neuropathol Exp Neurol , 2003 , 62 ( 2 ): 127 - 136 .
JIN R , YANG G , LI G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells [J]. J Leukoc Biol , 2010 , 87 ( 5 ): 779 - 789 .
张予阳 , 刘岩 , 付守廷 . 脑缺血与炎症反应 [J]. 中国药理学通报 , 2006 , 22 ( 1 ): 5 - 9 .
Berti R , Williams A J , Moffett J R , et al . Quantitative real-time RT-PCR analysis of inflammatory gene expression associated with ischemia-reperfusion brain injury [J]. J Cereb Blood Flow Metab , 2002 , 22 ( 9 ): 1068 - 1079 .
刘亭 , 刘香香 , 陈亭亭 , 等 . 灯盏细辛和赤芍配伍组方对大鼠脑缺血再灌注损伤的保护作用及对NF- κ B通路的影响 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 9 ): 111 - 115 .
Stephenson D , YIN T , Smalstig E B , et al . Transcription factor nuclear factor-kappa B is activated in neurons after focal cerebral ischemia [J]. J Cereb Blood Flow Metab , 2000 , 20 ( 3 ): 592 - 603 .
TU X K , YANG W Z , CHEN J P , et al . Curcumin inhibits TLR2/4-NF- κ B signaling pathway and attenuates brain damage in permanent focal cerebral ischemia in rats [J]. Inflammation , 2014 , 37 ( 5 ): 1544 - 1551 .
吴建良 , 沈敏敏 , 杨水新 , 等 . 阿魏酸对小胶质细胞炎性反应的抑制作用 [J]. 中国药理学通报 , 2015 , 31 ( 1 ): 97 - 102 .
孟锐 , 陈逸青 , 陈勤 . 阿魏酸对痴呆小鼠脑内胶质细胞活化与炎性细胞因子表达的影响 [J]. 中国医院药学杂志 , 2018 , 38 ( 1 ): 50 - 53 .
LIU Y M , SHEN J D , XU L P , et al . Ferulic acid inhibits neuro-inflammation in mice exposed to chronic unpredictable mild stress [J]. Int Immunopharmacol , 2017 , 45 : 128 - 134 .
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