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400016 重庆,重庆医科大学药学院,重庆市生物化学与分子药理重点实验室
[ 董志,E-mail: 100798@cqmu.edu.cn DONG Zhi, E-mail:100798@cqmu.edu.cn
收稿:2020-09-28,
修回:2020-10-27,
纸质出版:2021-02-15
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刘京东, 陈莎, 王钰淳, 等. β-石竹烯作用于Notch1/NF-κB信号轴对脑缺血再灌注损伤大鼠的改善作用[J]. 第三军医大学学报, 2021,43(3):218-225.
Jingdong LIU, Sha CHEN, Yuchun WANG, et al. β-caryophyllene improves cerebral ischemia reperfusion injury in rats
刘京东, 陈莎, 王钰淳, 等. β-石竹烯作用于Notch1/NF-κB信号轴对脑缺血再灌注损伤大鼠的改善作用[J]. 第三军医大学学报, 2021,43(3):218-225. DOI: 10.16016/j.1000-5404.202009067.
Jingdong LIU, Sha CHEN, Yuchun WANG, et al. β-caryophyllene improves cerebral ischemia reperfusion injury in rats
目的
2
探究β-石竹烯(β-caryophyllene,BCP)对脑缺血再灌注(cerebral ischemia-reperfusion,CIR)损伤大鼠的保护作用及相关机制。
方法
2
将SD大鼠按随机数字表法分为假手术组,缺血再灌注组,β-石竹烯低、中、高剂量组(分别为102、204、408 mg·kg
-1
),Jagged1+BCP对照组,Jagged1(Notch1激动剂)组。模型组、β-石竹烯低、中、高剂量组及Jagged1+BCP对照组、Jagged1组使用线栓法构建SD大鼠CIR模型,缺血1.5 h,再灌注48 h后,进行脑缺血梗死体积测定以及神经行为学评分,用Western blot检测脑组织中Notch1、NF-κB p65、NF-κB p-p65及Hes1蛋白表达;HE染色观察缺血侧海马中的细胞死亡数量;ELISA法检测大鼠缺血侧海马中TNF-α及IL1-β的含量变化。
结果
2
与模型组进行比较,BCP给药组可明显改善大鼠神经功能缺失,减少缺血侧脑梗死体积,降低海马中Notch1、NF-κB及Hes1的蛋白表达量(
P
<
0.05),减少TNF-α、IL-1β的释放(
P
<
0.05),减少海马神经元细胞的死亡数。与Jagged1干预组比较,BCP给药组Notch1的激动剂Jagged1可以拮抗BCP的治疗效果。
结论
2
BCP能够减轻大鼠的脑缺血再灌注损伤,可能通过抑制Notch1/NF-κB减少炎性因子的释放,发挥其缺血性保护作用。
Objective
2
To explore the protective effect of β-caryophyllene (BCP) on cerebral ischemia-reperfusion (I/R) rats and related mechanism.
Methods
2
SD rats were randomized into sham operation group
I/R group
and low-
medium- and high-dose BCP groups (102
204 and 408 mg·kg
-1
)
Jagged1 (Notch1 agonist
50 mg·kg
-1
in 3 h before I/R injury)+BCP group
and Jagged1 group. The treatments were given to the corresponding rats through intragastric infusion. In 7 d later
SD rat CIR model was established with suture-occlusion
with ischemia for 1.5 h followed by reperfusion for 48 h. The infarct volume and neurobehavioral s
core were measured; Western blotting was used to detect the cerebral protein levels of Notch1
NF-κB p65
NF-κB p-p65 and Hes1; HE staining was applied to observe the number of dead cells
and ELISA was employed to detect the changes of TNF-α and IL1-β contents in the ischemic hippocampus.
Results
2
BCP treatment could significantly improve the neurological deficit
reduce the infarct volume
down-regulate the protein levels of Notch1
NF-κB and Hes1 in the hippocampus (
P
<
0.05)
reduce the releases of TNF-α and IL-1β (
P
<
0.05)
and attenuate the death of hippocampal neuronal cells in the rats after cerebral I/R injury. Comparing the simple Jagged1 intervention group
Notch1 agonist
Jagged1
could antagonize the therapeutic effects of BCP.
Conclusion
2
BCP can attenuate cerebral I/R injury in rats
and exerts its protective effect probably through inhibiting Notch1/NF-κB signal axis to reduce the release of inflammatory factors.
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