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张艺,左丽婉,张启,伍昌总,刘春华.通窍定眩饮调节糖酵解改善脑缺血大鼠血管新生的机制研究[J].湖南中医药大学学报,2024,44(4):531-537[点击复制] |
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| 通窍定眩饮调节糖酵解改善脑缺血大鼠血管新生的机制研究 |
| 张艺,左丽婉,张启,伍昌总,刘春华 |
| (湖南中医药大学第二附属医院, 湖南 长沙 410005) |
| 摘要: |
| 目的 探究通窍定眩饮对脑缺血后血管新生的分子机制，并基于糖酵解通路探讨其可能的作用机制。方法 共40只大鼠，随机选取6只为假手术组，余采用大鼠大脑中动脉阻塞法建立脑缺血模型。24只造模成功的大鼠用随机分为模型组、丁苯酞组、联合用药组、通窍定眩饮组，每组6只。假手术组、模型组予蒸馏水10 mL/（kg·d）灌胃，丁苯酞组予丁苯酞54 mg/（kg·d）灌胃，联合用药组予丁苯酞54 mg/（kg·d）和中药药液14.6 g/（kg·d）灌胃，通窍定眩饮组予中药药液14.6 g/（kg·d）灌胃。干预3 d后采用Zea-Longa法观察大鼠的神经功能评分；TTC染色法确定脑损伤范围；ELISA法检测乳酸、腺苷三磷酸（adenosine triphosphate，ATP）和葡萄糖含量，免疫组化法检测葡萄糖转运蛋白1（glucose transporter 1，GLUT1）、己糖激酶2（hexokinase 2，HK2）、乳酸脱氢酶A （lactate dehydrogenase A，LDHA）蛋白的表达以及微血管密度变化。结果 与假手术相比，模型组有明显神经功能缺损，脑梗死体积比明显增加（P＜0.05），乳酸含量增加（P＜0.05），ATP和葡萄糖含量减少（P＜0.05），GLUT1、HK2、LDHA蛋白的表达增加（P＜0.05），微血管密度增加（P＜0.05）。与模型组相比，丁苯酞组神经功能缺损程度及脑梗死体积比明显降低（P＜0.05），乳酸、ATP和葡萄糖含量无显著变化（P＞0.05），GLUT1、HK2、LDHA蛋白的表达无显著变化（P＞0.05），微血管密度增加（P＜0.05）；联合用药组和通窍定眩饮组神经功能缺损程度及脑梗死体积比明显降低（P＜0.05），乳酸、ATP和葡萄糖含量均增加（P＜0.05），GLUT1、HK2、LDHA蛋白的表达及微血管密度显著增加（P＜0.05）。与联合用药组相比，丁苯酞组脑梗死体积比增加（P＜0.05），乳酸、ATP和葡萄糖含量减少（P＜0.05），GLUT1、HK2、LDHA蛋白的表达降低（P＜0.05），微血管密度降低（P＜0.05）；通窍定眩饮组脑梗死体积比增加（P＜0.05），乳酸、ATP和葡萄糖含量无显著变化（P＞0.05），GLUT1、HK2、LDHA蛋白的表达无显著变化（P＞0.05），微血管密度降低（P＜0.05）。结论 通窍定眩饮对脑缺血模型具有一定的神经保护作用，其机制可能与调控糖酵解通路促进血管新生有关。 |
| 关键词: 通窍定眩饮 糖酵解 脑缺血 血管新生 葡萄糖转运蛋白1 己糖激酶2 乳酸脱氢酶A |
| DOI：10.3969/j.issn.1674－070X.2024.04.001 |
| 投稿时间：2023-10-12 |
| 基金项目:湖南省教育厅科研项目（22A0269）；湖南省研究生科研创新项目（CX20220818）。 |
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| Mechanism of Tongqiao Dingxuan Decoction regulating glycolysis to improve angiogenesis in rats with cerebral ischemia |
| ZHANG Yi,ZUO Liwan,ZHANG Qi,WU Changzong,LIU Chunhua |
| (The Second Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China) |
| Abstract: |
| Objective To explore the molecular mechanism of Tongqiao Dingxuan Decoction (TQDXD) on cerebral ischemia-induced angiogenesis,and to discuss its possible mechanism of action based on the glycolysis pathways.Methods A total of 40 rats were used,six rats were randomly selected as sham-operated group,and the rest were used to establish a cerebral ischemia model by the method of middle cerebral artery occlusion.Twenty-four rats with successful modeling were randomized into model,butylphthalide,combination,and TQDXD groups,with six rats in each group.Sham-operated and model groups were treated with distilled water 10 mL/(kg·d),butylphthalide group with butylphthalide 54 mg/(kg·d),combination group with butylphthalide 54 mg/(kg·d) and TQDXD 14.6 g/(kg·d),and TQDXD group with TQDXD 14.6 g/(kg·d).All the drugs and distilled water were administered by gavage.After 3 d of intervention,the neurological function of the rats was scored using the Zea-Longa method;the extent of cerebral infarction was determined by TTC staining;the levels of lactate,adenosine triphosphate (ATP),and glucose were measured by ELISA;the protein expressions of glucose transporter 1(GLUT1),hexokinase 2(HK2),and lactate dehydrogenase A (LDHA),as well as changes in microvessel density were examined by immunohistochemistry.Results Compared with the sham-operated group,the model group exhibited significant neurological deficits and obviously increased volume ratio of cerebral infarction (P＜0.05),elevated lactate level (P＜0.05),decreased ATP and glucose levels (P＜0.05),higher protein expressions of GLUT1,HK2,and LDHA (P＜0.05),and increased microvessel density (P＜0.05).Compared with the model group,the butylphthalide group showed significantly reduced neurological deficits and volume ratio of cerebral infarction (P＜0.05),and increased microvessel density (P＜0.05),with no significant changes in lactate,ATP,and glucose levels (P＞0.05),nor in the protein expressions of GLUT1,HK2,and LDHA (P＞0.05);both the combination and TQDXD groups showed significantly reduced neurological deficits and volume ratio of cerebral infarction (P＜0.05).increased lactate,TP,and glucose levels (P＜0.05),and significantly elevated protein expressions of GLUT1,HK2,and LDHA,and microvessel density (P＜0.05).Compared with the combination group,the butylphthalide group exhibited increased cerebral infarction area (P＜0.05),decreased lactate,ATP,and glucose levels (P＜0.05),lower protein expressions of GLUT1,HK2,and LDHA (P＜0.05),and reduced microvessel density (P＜0.05);the TQDXD group showed increased cerebral infarction area (P＜0.05) and decreased microvessel density (P＜0.05),with no significant changes in the levels of lactate,ATP,and glucose (P＞0.05),nor in the protein expressions of GLUT1,HK2,and LDHA (P＞0.05).Conclusion TQDXD has a certain neuroprotective effect on cerebral ischemia model,and its mechanism may be related to regulating glycolysis pathways to promote angiogenesis. |
| Key words: Tongqiao Dingxuan Decoction glycolysis cerebral ischemia angiogenesis glucose transporter 1 hexokinase 2 lactate dehydrogenase A |
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