W026B对大鼠全脑缺血再灌注损伤的保护作用

doi:10.5246/jcps.2022.02.009

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (2): 108-116.DOI: 10.5246/jcps.2022.02.009

W026B对大鼠全脑缺血再灌注损伤的保护作用

王子翼¹, 刘晓岩¹, 朱元军¹, 刘晔², 张平平², 王银叶¹^,^*()

1. 北京大学医学部药学院分子与细胞药理学系, 北京 100191
2. 北京红惠新医药科技有限公司, 北京 102600

收稿日期:2021-10-26 修回日期:2021-11-07 接受日期:2021-12-05 出版日期:2022-02-27 发布日期:2022-02-25
通讯作者: 王银叶
作者简介:
+ Tel.: +86-10-82802652, E-mail: wangyinye@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81503060, 81573333), and R&D Foundation of Beijing Honghui New Medical Technology Co., Ltd.

The protective effect of W026B on global cerebral ischemia/reperfusion injury model in rats

Ziyi Wang¹, Xiaoyan Liu¹, Yuanjun Zhu¹, Ye Liu², Pingping Zhang², Yinye Wang¹^,^*()

1 Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2 Beijing Honghui New Medical Technology Co., Ltd., Beijing Daxing Biological Medicine Industry Base, Beijing 102600, China

Received:2021-10-26 Revised:2021-11-07 Accepted:2021-12-05 Online:2022-02-27 Published:2022-02-25
Contact: Yinye Wang

摘要/Abstract

摘要：

脑缺血在世界范围内严重影响着人类的生活质量和生命健康。W026B是一种新合成的木脂素衍生物, 对局灶性脑缺血/再灌注模型具有保护作用, 但W026B对全脑缺血/再灌注(GCI/R)模型是否具有脑保护作用尚不清楚。本文研究了W026B对四血管闭塞性全脑缺血再灌注模型是否具有脑保护作用。结果显示: W026B明显提高了GCI/R后7天的大鼠存活率, 显著改善了GCI/R后7天内的神经功能缺陷评分, 明显增强了GCI/R大鼠海马中存活神经元的数量。此外, W026B明显降低了GCI/R大鼠海马组织中ROS的水平, 并增加了SOD的活性; 明显降低NF-κB p65的表达和IL-6的水平, W026B也降低了caspase-3的活性。这些结果首次证明了W026B对GCI/R大鼠具有脑保护作用, 其作用可能与抑制GCI/R过程中的氧化应激、炎症反应和细胞凋亡有关。本研究为W026B对脑缺血/再灌注损伤的保护作用提供了新证据。

关键词: 全脑缺血/再灌注, W026B, 神经行为学, 氧化应激, 炎症, 凋亡

Abstract:

Cerebral ischemia seriously affects the quality of life and health of human worldwide. W026B is a newly synthesized lignan derivative that has a protective effect on the focal cerebral ischemia/reperfusion model, while it is unclear whether W026B has a cerebral protective effect on the model of global cerebral ischemia/reperfusion (GCI/R). In this study, we investigated the protective effect of W026B on the four-vessel occlusion GCI/R model. The results showed that W026B obviously increased the survival rate of rats during 7 d after GCI/R and significantly improved neurological deficits within 7 d after GCI/R. It evidently enhanced the number of survival neurons in the hippocampus of GCI/R rats. Furthermore, W026B notably lowered the level of ROS, and increased the activity of SOD in the hippocampus of GCI/R rats. Moreover, it also decreased the expression of NF-κB p65 and the level of IL-6 apparently. In addition, W026B evidently lowered the activity of caspase-3. In conclusion, this study firstly proves that W026B has the protective effect on GCI/R rats. Its cerebral protective effect maybe related to the inhibition of oxidative stress, inflammatory response, and cell apoptosis during GCI/R. These results provide new evidence with the protective effect of W026B on cerebral ischemia/reperfusion injury.

Key words: Global cerebral ischemia/reperfusion, W026B, Neurobehavior, Oxidative stress, Inflammation, Apoptosis

Supporting:

王子翼, 刘晓岩, 朱元军, 刘晔, 张平平, 王银叶. W026B对大鼠全脑缺血再灌注损伤的保护作用[J]. 中国药学(英文版), 2022, 31(2): 108-116.

Ziyi Wang, Xiaoyan Liu, Yuanjun Zhu, Ye Liu, Pingping Zhang, Yinye Wang. The protective effect of W026B on global cerebral ischemia/reperfusion injury model in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(2): 108-116.

图/表 6

Figure 1. Effect of W026B on survival rate in GCI/R rats. Rats used in each group: n = 12 in the sham group, n = 20 in the vehicle group, n = 13 in the W026B50 group, n = 14 in the W026B250 group, n = 16 in the NBP group. ^^P < 0.01 versus sham group, *P < 0.05 versus vehicle group.

Figure 2. Effect of W026B on neurological scores in GCI/R rats. (A) Standing upright times in an empty box. (B) Inclined beam walking scores. n = 10, *P < 0.05, **P < 0.01, ***P < 0.001 versus vehicle group, ^P < 0.05 versus NBP group.

Figure 3. Effect of W026B on pyramidal neurons in hippocampal CA1. (A) Nissl staining of hippocampal CA1 in GCI/R rats on day 8. (B) Viable neuron number in hippocampal CA1 in GCI/R rats. n = 7–8, **P < 0.01, ***P < 0.001 versus vehicle group, ^^P < 0.01 versus NBP group.

Figure 4. Effect of W026B on oxidative stress in hippocampus in GCI/R rats. (A) The level of ROS in the hippocampus. (B) SOD activity in hippocampus. n = 4–6, *P < 0.05, **P < 0.01 versus vehicle group.

Figure 5. Effect of W026B on inflammation-related factors in hippocampus in GCI/R rats. (A) The expression of NF-κB p65 in hippocampus, n = 3. (B) The level of IL-6 in hippocampus, n = 5. ^^^P < 0.001 versus sham group, *P < 0.05 versus vehicle group.

Figure 6. Effect of W026B on caspase-3 activity in hippocampus in GCI/R rats. n = 4, ^^P < 0.01 versus sham group, *P < 0.05 versus vehicle group.

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W026B对大鼠全脑缺血再灌注损伤的保护作用

The protective effect of W026B on global cerebral ischemia/reperfusion injury model in rats

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