博舒替尼对大鼠脑缺血/再灌注损伤的影响*

doi:10.12047/j.cjap.6327.2022.146

中国应用生理学杂志 ›› 2022, Vol. 38 ›› Issue (6): 803-806.doi: 10.12047/j.cjap.6327.2022.146

博舒替尼对大鼠脑缺血/再灌注损伤的影响^*

张艺¹, 吴超², 张奇³, 孔钰⁴, 卞晓倩⁵, 王影⁵, 李曙^2△

1.皖南医学院研究生学院;
2.皖南医学院基础医学院, 安徽芜湖 241000;
3.芜湖市第二人民医院老年医学科, 安徽芜湖 241000;
4.皖南医学院公共卫生学院;
5.皖南医学院临床医学院, 安徽芜湖 241000

收稿日期:2022-06-14 修回日期:2022-11-17 出版日期:2022-11-28 发布日期:2023-06-12
通讯作者: ^△Tel: 0553-3932681; E-mail: wylishu@wnmc.edu.cn
基金资助:
^*安徽省高校科学研究重大项目(KJ2020ZD55);2022年高校优秀拔尖人才培育资助项目(gxgnfx2020090);皖南医学院中青年课题(WK202001, WK202102);安徽省大学生创新创业训练计划(S202110368054)

Effects of Bosutinib on cerebral ischemia/reperfusion injury in rats

ZHANG Yi¹, WU Chao², ZHANG Qi³, KONG Yyu⁴, BIAN Xiao-qian⁵, WANG Ying⁵, LI Shu^2△

1. Graduate School, Wannan Medical College,
2. Basic Medical School, Wannan Medical College, Wuhu 241000;
3. Geriatrics,Wuhu Second People's Hospital, Wuhu 241000;
4. School of Public Health, Wannan Medical College,
5. Clinical College, Wannan Medical College, Wuhu 241000, China

Received:2022-06-14 Revised:2022-11-17 Online:2022-11-28 Published:2023-06-12

摘要/Abstract

摘要： 目的: 探索博舒替尼(Bosutinib)对大鼠脑缺血/再灌注损伤早期的干预作用。方法: 40只SD大鼠随机分成4组(随机数字法),每组10只, 设sham组(对照组):只分离颈部血管,不做其他处理;MCAO(模型组):采用改良线栓法制作大鼠脑缺血/再灌注损伤模型,缺血2 h后再灌注24 h;DMSO组(溶剂组):实验前1 d尾静脉注射溶剂DMSO( 0.752 ml/kg),脑缺血2 h再灌24 h;Bosutinib组(干预组);实验前1 d予以尾静脉注射现配的Bosutinib(4 mg/kg),脑缺血2 h再灌24 h。缺血/再灌注24 h后,进行神经功能评分;用TTC染色后计算脑梗死面积;Western blot法检测SIK2蛋白表达水平;ELISA检测脑组织中细胞因子TNF-α、IL-6含量。结果: 神经功能评分,与 sham 组比较,MCAO 及DMSO组的评分显著升高 (P＜0.05);与 MCAO 及DMSO 两组比较,Bosutinib 组的评分显著下降 (P＜0.05)。脑梗死体积,与sham组对比,MCAO及DMSO组梗死体积百分比均显著增大 (P＜0.01);与MCAO及DMSO两组相比较,Bosutinib组脑梗死体积百分比显著减少(P＜0.01)。SIK2的蛋白表达,与sham组比较,MCAO及DMSO组的SIK2蛋白表达无显著变化(P＞0.05);与MCAO及DMSO比较, Bosutinib组SIK2蛋白表达显著下降(P＜0.05)。炎症因子变化,与sham组对比,MCAO组及DMSO组的IL-6、TNF-α含量均显著升高(P＜0.05);与MCAO组及DMSO组比较,Bosutinib组IL-6、TNF-α含量均显著下降(P＜0.05)。结论: Bosutinib可减少脑缺血/再灌注引起的损伤,其可能机制与抑制SIK2蛋白及炎症因子的表达有关。

关键词: 博苏替尼, 脑缺血/再灌注损伤, SIK2, 炎症

Abstract: Objective: To investigate the effects of bosutinib on the early stage of cerebral ischemia-reperfusion injury in rats. Methods: Forty Sprague-Dawley rats were randomly divided into four groups (random number method), 10 rats in each group; sham group (control group): only neck vessels were isolated without other treatments; MCAO (model group): the rat brain ischemia/reperfusion injury model was made by a modified wire bolus method,ischemia for 2 h followed by reperfusion for 24 h; DMSO group (solvent group): DMSO ( 0.752 ml/kg) was injected into the tail vein one day before the experiment, brain ischemia 2 h reperfusion for 24 h; Bosutinib group (intervention group): one day before the experiment, the tail vein was injected with Bosutinib (4 mg/kg), brain ischemia 2 h reperfusion for 24 h. After 24 h of ischemia reperfusion, neurological function score was performed; brain infarct area was calculated after staining with TTC; SIK2 was detected by Western blot; the contents of TNF-α and IL-6 in brain tissue were detected by ELISA. Results: Compared with the sham group, the neurological function scores, the infarct volume percentages and the levels of inflammatory factors IL-6 and TNF-α of the MCAO and DMSO groups were increased significantly (P＜0.05 or P＜0.01). Compared with the MCAO and DMSO groups, the above mentioned indexes of the bosutinib group were all decreased significantly (P＜0.05 or P＜ 0.01). Compared with sham group, the expression levels of SIK2 protein in MCAO and DMSO groups had no significant changes(P＞ 0.05); compared with the MCAO and DMSO group, the expression level of SIK2 protein in the bosutinib group was decreased significantly (P＜0.05). Conclusion: Bosutinib reduces cerebral ischemia-reperfusion-induced injury, and its possible mechanism is related to the decreased expression of SIK2 protein and inflammatory factors.

Key words: Bosutinib, cerebral ischemia-reperfusion injury, SIK2, inflammation

中图分类号:

R743.3

张艺, 吴超, 张奇, 孔钰, 卞晓倩, 王影, 李曙. 博舒替尼对大鼠脑缺血/再灌注损伤的影响^*[J]. 中国应用生理学杂志, 2022, 38(6): 803-806.

ZHANG Yi, WU Chao, ZHANG Qi, KONG Yyu, BIAN Xiao-qian, WANG Ying, LI Shu. Effects of Bosutinib on cerebral ischemia/reperfusion injury in rats[J]. CJAP, 2022, 38(6): 803-806.

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博舒替尼对大鼠脑缺血/再灌注损伤的影响^*

Effects of Bosutinib on cerebral ischemia/reperfusion injury in rats

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