中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (28): 4535-4540.doi: 10.12307/2024.467

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

天麻素干预可减轻缺血性脑卒中大鼠的炎症损伤

关金琦1,孙萍萍2,边  静2,闫  雪2,张为民2   

  1. 1长春中医药大学,吉林省长春市  130117;2长春中医药大学附属第三临床医院,吉林省长春市  130021
  • 收稿日期:2023-07-21 接受日期:2023-08-30 出版日期:2024-10-08 发布日期:2023-11-27
  • 通讯作者: 张为民,硕士,主任医师,教授,博士生导师,长春中医药大学附属第三临床医院,吉林省长春市 130021
  • 作者简介:关金琦,女,1998年生,吉林省通化市人,满族,长春中医药大学在读硕士,主要从事神经疾病的中医康复研究。
  • 基金资助:
    国家重点研发计划(2018YFC1706003),项目参与人:张为民;吉林省科技发展计划(20230203092SF),项目负责人:张为民

Gastrodin intervention attenuates inflammatory injury in ischemic stroke rats

Guan Jinqi1, Sun Pingping2, Bian Jing2, Yan Xue2, Zhang Weimin2   

  1. 1Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China; 2The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China
  • Received:2023-07-21 Accepted:2023-08-30 Online:2024-10-08 Published:2023-11-27
  • Contact: Zhang Weimin, Master, Chief physician, Professor, Doctoral supervisor, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China
  • About author:Guan Jinqi, Master candidate, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
  • Supported by:
    the National Key Research and Development Program of China, No. 2018YFC1706003 (to ZWM [project participant]); Jilin Province Science and Technology Development Plan, No. 20230203092SF (to ZWM)

摘要:


文题释义:

天麻素:又称天麻苷,是中药天麻的主要生物活性成分。自1978年发现以来,天麻素的药理学特性得到了广泛的研究,目前天麻素主要用于治疗中枢神经系统疾病,如缺血性脑卒中、癫痫、阿尔茨海默病等,其作用机制主要包括抗炎、抗氧化、调节神经递质、抑制小胶质细胞活化、上调神经营养因子等。
炎症:是机体对于刺激的一种防御反应,主要表现为红、肿、热、痛和功能障碍,一般是由于免疫系统疾病、癌症、感染或神经系统疾病等引起。


背景:天麻素具有抗炎作用,在临床中主要用于治疗缺血性脑卒中,目前其作用机制尚不明确。

目的:探讨天麻素干预缺血性脑卒中大鼠炎症损伤的作用机制。 
方法:将50只SD大鼠采用随机数字法分为假手术组、模型组、阳性对照组、天麻素高剂量组和天麻素低剂量组,每组10只。除假手术组外,其余4组大鼠均采用大鼠中脑动脉闭塞法建立缺血性脑卒中模型。各组于术后第3天开始给药,阳性对照组大鼠腹腔注射依达拉奉注射液(6 mg/kg),天麻素高剂量组和天麻素低剂量组大鼠腹腔注射天麻素注射液(50,10 mg/kg),假手术组和模型组大鼠腹腔注射等体积生理盐水。各组连续治疗14 d后,观察大鼠脑组织的病理变化,检测NLRP3炎症小体阳性表达及炎症反应相关蛋白和mRNA表达。

结果与结论:①与假手术组相比,模型组大鼠脑梗死体积变大;脑组织结构疏松,可见不规则空洞,神经元数量减少并排列不规则;NLRP3炎症小体阳性表达上升(P < 0.01);Toll样受体4、髓样分化因子88、凋亡相关斑点样蛋白、半胱氨酸蛋白酶1、白细胞介素1β蛋白及mRNA表达水平上升(P < 0.01);②与模型组相比,天麻素高剂量组和天麻素低剂量组大鼠脑梗死体积变小,神经元排列规则,数量增加,分布均匀;天麻素高剂量组NLRP3炎症小体阳性表达下降(P < 0.05);天麻素高剂量组Toll样受体4、髓样分化因子88、凋亡相关斑点样蛋白、半胱氨酸蛋白酶1、白细胞介素1β 蛋白和mRNA表达下降(P < 0.01);天麻素低剂量组Toll样受体4蛋白表达无显著差异,其余炎症反应相关因子的蛋白和mRNA表达下降(P < 0.05,P < 0.01);③结果表明,天麻素干预可减轻缺血性脑卒中大鼠的炎症损伤,其作用机制可能与抑制炎症反应相关因子表达有关。

https://orcid.org/0009-0004-4235-4306(张为民)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 缺血性脑卒中, 天麻素, NLRP3, 炎症反应, 炎症因子, 大鼠

Abstract: BACKGROUND: Gastrodin has anti-inflammatory effects and is mainly used in clinical practice for the treatment of ischemic stroke, and its mechanism of action is still unclear.
OBJECTIVE: To explore the mechanism of gastrodin intervention on inflammatory injury in ischemic stroke rats.
METHODS: Fifty Sprague-Dawley rats were divided into sham-operated group, model group, positive control group, high-dose gastrodin group and low-dose gastrodin group by the randomized numerical method, with 10 rats in each group. Ischemic stroke models were established by the middle cerebral artery occlusion method in all groups of rats except for the sham operation group. Administration in each group started on the 3rd day after surgery, and the rats in the positive control group were intraperitoneally injected with edaravone injection (6 mg/kg), the rats in the high- and low-dose gastrodin groups were intraperitoneally injected with 50 and 10 mg/kg gastrodin injection respectively, and the rats in the sham-operated and model groups were intraperitoneally injected with the equal volume of physiological saline. After 14 days of continuous treatment in each group, the pathological changes in rat brain tissue were observed, and the positive expression of NLRP3 inflammasome and the expression of inflammatory response-related proteins and their mRNAs were detected.
RESULTS AND CONCLUSION: Compared with the sham-operated group, the volume of cerebral infarction became larger in the model group; the structure of brain tissue was loose, irregular cavities could be observed, and the number of neurons was reduced and irregularly arranged; the positive expression of NLRP3 inflammasome increased (P < 0.01); and the protein and mRNA expression levels of Toll-like receptor 4, myeloid differentiation factor 88, apoptosis-associated speck-like protein containing a caspase-recruitment domain, Caspase-1, and interleukin-1β increased (P < 0.01). Compared with the model group, the volume of cerebral infarction became smaller in the high- and low-dose gastrodin groups; the neurons were regularly arranged, increased in number, and uniformly distributed; the positive expression of NLRP3 inflammasome was decreased (P < 0.05); the protein and mRNA expression levels of Toll-like receptor 4, myeloid differentiation factor 88, apoptosis-associated speck-like protein containing a caspase-recruitment domain, Caspase-1, and interleukin-1β were decreased in the high-dose gastrodin group (P < 0.01); Toll-like receptor 4 protein expression showed no significant changes in the low-dose gastrodin group, and the protein and mRNA expression of the other inflammatory response-associated factors decreased (P < 0.05, P < 0.01). To conclude, gastrodin attenuates inflammatory injury in ischemic stroke rats, and its mechanism of action may be related to the inhibition of inflammatory response-associate factor expression.

Key words: ischemic stroke, gastrodin, NLRP3, inflammation response, inflammatory factor, rat

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