β-caryophyllene alleviates ischemic stroke injury by upregulating neuronal miR-183 expression in mice

Yuchun WANG; Jingdong LIU; Sha CHEN; Daohang LIU; Zhi DONG

doi:10.16016/j.1000-5404.202004017

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β-caryophyllene alleviates ischemic stroke injury by upregulating neuronal miR-183 expression in mice

Neurosciences | 更新时间：2026-01-09

- β-caryophyllene alleviates ischemic stroke injury by upregulating neuronal miR-183 expression in mice
- Journal of Third Military Medical University Vol. 42, Issue 16, Pages: 1625-1632(2020)
- 作者机构：
  
  1.400016 重庆，重庆医科大学药学院生物化学与分子药理学重点实验室
  2.200433 上海，复旦大学药学院
- 作者简介：
- 基金信息：
  
  the Project of Basic Research and Frontier Exploration of Chongqing(CSTC2018jcyjAX0378)
- DOI：10.16016/j.1000-5404.202004017
  CLC： R282.71;R743.3;R966
- Received：02 April 2020，
  
  Revised：2020-05-08，
  
  Published：30 August 2020
- 稿件说明：
移动端阅览
Yuchun WANG, Jingdong LIU, Sha CHEN, et al. β-caryophyllene alleviates ischemic stroke injury by upregulating neuronal miR-183 expression in mice[J]. Journal of Third Military Medical University, 2020, 42(16): 1625-1632.
DOI：

Yuchun WANG, Jingdong LIU, Sha CHEN, et al. β-caryophyllene alleviates ischemic stroke injury by upregulating neuronal miR-183 expression in mice[J]. Journal of Third Military Medical University, 2020, 42(16): 1625-1632. DOI： 10.16016/j.1000-5404.202004017.

摘要

目的

探讨β-石竹烯(β-caryophyllene

BCP)是否对缺血性中风有保护作用，以及这种保护作用是否与miR-183和NF-κB的表达有关。

方法

在动物实验中，将90只C57BL/6雄性小鼠(20~25 g)编号后，根据随机数字法分为3组(

=30):假手术组、模型组、BCP(72 mg/kg)组。模型组和BCP(72 mg/kg)预处理组中动脉栓塞1 h后，再灌注24 h，构建小鼠缺血性中风模型。对小鼠进行神经行为学评分，TTC法测量小鼠脑梗死体积，HE染色和Nissl染色切片观察小鼠大脑神经元、炎性细胞和凋亡小体的病理变化，检测miR-183、NF-κB、p-NF-κB、白介素-1β(IL-1β)、白介素-6(IL-6)的表达，双荧光素酶标记法检测miR-183与NF-κB的靶向关系。提取小鼠的原代神经元，分为3组:正常组、糖氧剥夺(oxygen-glucose deprivation，OGD)损伤组、BCP(10 μmol/L)组。OGD损伤组与BCP(10 μmol/L)预处理组神经元糖氧剥夺1 h后，正常培养24 h，构建神经元缺血性中风模型。观察神经元形态和数量的变化，测定细胞损伤率，测定神经元内miR-183、NF-κB和p-NF-κB的表达，检测炎性因子在神经元内的表达。

结果

动物实验中，与假手术组相比，模型组小鼠神经行为出现障碍，脑梗死体积增大(

0.05)。脑组织切片HE染色和Nissl染色显示，缺血一侧的神经元等细胞受到严重损伤。同时，miR-183的表达下降(

0.05)，NF-κB被活化成p-NF-κB，炎性因子NF-κB、IL

-1β和IL-6表达升高(

0.05)。与模型组相比，BCP预处理能改善造模后小鼠神经行为障碍，减少脑梗死体积，保护神经元的形态，减少炎性细胞和凋亡小体的数量，增加皮质中的尼氏阳性细胞数量(

0.05)。BCP预处理上调miR-183的表达，抑制NF-κB的活化，降低炎性因子的表达(

0.05)。在神经元实验中，OGD后神经元受损严重，而BCP预处理则保护了神经元，降低神经元死亡率(

0.05)。BCP预处理还上调神经元中miR-183的表达，抑制NF-κB的活化，降低神经元中炎性因子的表达(

0.05)。

结论

缺血性中风后，BCP可能通过上调miR-183表达进一步抑制NF-κB的活化，减少炎性因子释放，从而减轻炎症，发挥脑保护作用。

Abstract

Objective

To investigate the protective effect of β-caryophyllene (BCP) against ischemic stroke injury in mice and clarify whether such protective effects are associated with miR-183 and nuclear factor-κB (NF-κB) expression.

Methods

Ninety male C57BL/6 mice were randomized equally into 3 groups

namely the sham-operated group

ischemia-reperfusion (I/R) model group

and BCP (72 mg/kg) pretreatment group. The mice in the latter 2 groups were subjected to middle cerebral artery occlusion for 60 min followed by reperfusion for 24 h. The neurological deficits and infarct volume of the mice were measured

and the pathological changes in the brain tissues were observed using HE and Nissl staining. The expression of miR-183

NF-κB

p-NF-κB

interleukin-1β (IL-1β)

and IL-6 in the brain were detected

and the targeting relationship between miR-183 and NF-κB was determined. In the

in vitro

experiment

the cortical neurons isolated from the brain of neonatal mice were divided into normal group

oxygen-glucose deprivation (OGD) group

and OGD group with 10 μmol/L BCP pretreatment. Immunofluorescence assay was employed for morphological observation of the neurons

and the cell injury was assessed with lactate dehydrogenase (LDH) leakage assay. The expression levels of miR-183

IL-1β

IL-6 and NF-κB in the neurons were measured.

Results

In the mouse models of ischemic stroke

BCP pretreatment significantly improved neurologic deficit score

reduced the infarct volume

lessened pathological changes of the brain tissue

and decreased the number of Nissl-positive cells in the cortex (

0.05). BCP pretreatment significantly upregulated the expression of miR-183 in the brain tissues of the mice (

0.05). In the

in vitro

experiment

BCP pretreatment produced obvious protective effect on neurons and significantly lowered neuronal death rate following OGD (

0.05). BCP treatment significantly upregulated the expression of miR-183

inhibited NF-κB activation and lowered the expressions of inflammatory factors in the neurons (

0.05).

Conclusion

BCP protects the brain tissues against ischemic stroke injury by upregulating the expression of miR-183

which inhibits NF-κB activation and lowers the release of inflammatory factors to alleviate inflammation in the brain.

关键词

Keywords

references

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