Shuxuetong Inhibits Bim-dependent Apoptosis of Cerebellar Granule Neurons

PAN Shenhao; CAO Dongfang; ZHAO Fanyi; ZHAO Sijie; ZHANG Chenghao; LIANG Jianfeng; WU Jianwei; YUAN Zhongmin

doi:10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240711.003

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Shuxuetong Inhibits Bim-dependent Apoptosis of Cerebellar Granule Neurons

Preclinic Research | 更新时间：2024-07-30

- Shuxuetong Inhibits Bim-dependent Apoptosis of Cerebellar Granule Neurons
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 45, Issue 4, Pages: 549-556(2024)
- 作者机构：
  
  1.广州医科大学第二临床学院，广东广州510260
  2.广州医科大学附属第二医院神经科学研究所，广东广州510260
  3.广州医科大学附属第二医院番禺院区神经外科，广东广州511400
- 作者简介：
  
  YUAN Zhongmin； E-mail： yzm@gzhmu.edu.cn
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240711.003
  CLC： R741
- Published：20 July 2024，
  
  Received：20 May 2024，
  
  Accepted：23 June 2024
- 稿件说明：
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潘甚豪,曹东芳,赵凡一等.疏血通抑制Bim依赖的小脑颗粒神经元凋亡[J].中山大学学报（医学科学版）,2024,45(04):549-556.

PAN Shenhao,CAO Dongfang,ZHAO Fanyi,et al.Shuxuetong Inhibits Bim-dependent Apoptosis of Cerebellar Granule Neurons[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(04):549-556.
潘甚豪,曹东芳,赵凡一等.疏血通抑制Bim依赖的小脑颗粒神经元凋亡[J].中山大学学报（医学科学版）,2024,45(04):549-556. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240711.003.

PAN Shenhao,CAO Dongfang,ZHAO Fanyi,et al.Shuxuetong Inhibits Bim-dependent Apoptosis of Cerebellar Granule Neurons[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(04):549-556. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240711.003.

摘要

目的

探究疏血通及其主要成分水蛭素对Sprague-Dawley（SD）大鼠小脑颗粒神经元（CGNs）凋亡的影响及机制。

方法

体外成熟7 d的CGNs分为存活对照组（用含K

浓度为25 mmol/L的培养基，即25 K组）、凋亡组（用含K

浓度为5 mmol/L的培养基，即5 K组）、以1/50、1/40、1/30、1/20、1/10浓度（稀释50、40、30、20、10倍）疏血通注射液处理组（25 K以及5 K合并疏血通处理组）以及对应不同浓度（2 U/mL、2.5 U/mL、3.34 U/mL、5 U/mL、10 U/mL）水蛭素处理组（25 K以及5 K合并水蛭素处理组），用Hoechst染色法观察并统计凋亡率。在蛋白印迹实验中，在25 K和5 K条件下用1/50、1/10浓度疏血通注射液以及对应2 U/mL、10 U/mL浓度水蛭素处理细胞，用Western blot法检测Cleaved Caspase-3、Bim、VEGF的表达水平。

结果

核染色结果显示，与25 K存活对照组比较，5 K凋亡组凋亡率增加；与25 K存活对照组比较，不同浓度疏血通注射液与水蛭素处理细胞后凋亡率无明显变化；与5 K凋亡组比较，不同浓度疏血通注射液与水蛭素处理细胞后凋亡率下降，且随着浓度的升高，凋亡率下降越明显。Western blot结果显示，与5 K凋亡组比较，不同浓度疏血通与水蛭素处理细胞后Cleaved Caspase-3、Bim蛋白表达水平均下降，VEGF蛋白表达水平升高。

结论

疏血通及其主要成分水蛭素通过抑制Bim表达，进而抑制线粒体依赖的小脑颗粒神经元凋亡。

Abstract

Objective

To investigate the effect and mechanism of Shuxuetong and its main component hirudin on the apoptosis of cerebellar granule neurons （CGNs） in Sprague-Dawley（SD） rats.

Methods

CGNs incubated in vitro for 7 days were divided into survival control group or 25 K group （cultured in medium containing 25 mmol/L KCL） and apoptosis group or 5 K group （cultured in medium containing 5 mmol/L KCL）. CGNs were separately treated with proportionally diluted and different concentrations of Shuxuetong （1/50， 1/40， 1/30， 1/20 and 1/10） and the corresponding different concentrations of hirudin （2， 2.5， 3.34， 5 and 10 U / mL）. Hoechst staining was performed to analyze the apoptosis. Western blot was used to detect the expression levels of Cleaved Caspase-3， Bim and VEGF.

Results

Hoechst staining showed that 5 K group had a higher apoptosis rate than 25 K group. In 25 K group， there was no significant change in the apoptosis rate between neurons treated with different concentrations of Shuxuetong and hirudin， but significant changes was found in 5 K group and the higher the concentration， the lower the apoptosis rate. Western blot results revealed that， compared with control neurons in 5 K group， Shuxuetong injection and hirudin treatments resulted in a decrease of Cleaved Caspase-3 and Bim expression， but an increase of VEGF protein.

Conclusions

Shuxuetong and its main component hirudin inhibits the apoptosis of CGNs through suppressing proapoptotic BH3-only protein Bim.

关键词

小脑颗粒神经元凋亡疏血通水蛭素Bim血管内皮生长因子

Keywords

cerebellar granule neuronsapoptosisshuxuetonghirudinBimVEGF

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