中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (11): 2327-2333.doi: 10.12307/2025.349

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

汉黄芩素干预糖尿病脑梗死模型大鼠的神经损伤

王欢欢1，梁盼盼1，杨金水1，贾淑贤2，赵佳佳1，陈媛媛1，薛  茜1，宋爱霞1   

  1. 河北北方学院附属第一医院，1神经内科，2老年病科，河北省张家口市  075000
  • 收稿日期:2024-03-28 接受日期:2024-05-17 出版日期:2025-04-18 发布日期:2024-08-12
  • 通讯作者: 宋爱霞，硕士生导师，主任医师，河北北方学院附属第一医院神经内科，河北省张家口市 075000
  • 作者简介:王欢欢，女，1989年生，汉族，河北省衡水市人，硕士，主治医师，主要从事缺血性脑血管病方面的研究。
  • 基金资助:
    河北省医学科学研究基金(20220584)，项目负责人：王欢欢；张家口市科技计划基金(2121183D)，项目负责人：王欢欢

Effect of wogonin on nerve injury in rats with diabetic cerebral infarction

Wang Huanhuan1, Liang Panpan1, Yang Jinshui1, Jia Shuxian2, Zhao Jiajia1, Chen Yuanyuan1, Xue Qian1, Song Aixia1   

  1. 1Department of Neurology, 2Department of Geriatrics, Hebei North University Affiliated First Hospital, Zhangjiakou 075000, Hebei Province, China
  • Received:2024-03-28 Accepted:2024-05-17 Online:2025-04-18 Published:2024-08-12
  • Contact: Song Aixia, Master’s supervisor, Chief physician, Department of Neurology, Hebei North University Affiliated First Hospital, Zhangjiakou 075000, Hebei Province, China
  • About author:Wang Huanhuan, Master, Attending physician, Department of Neurology, Hebei North University Affiliated First Hospital, Zhangjiakou 075000, Hebei Province, China
  • Supported by:
    the Medical Science Research Fund of Hebei Province, No. 20220584 (to WHH); Science and Technology Program Fund of Zhangjiakou City, No. 2121183D (to WHH)

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摘要：


文题释义：
糖尿病脑梗死：糖尿病是最常见的慢性代谢综合征，研究发现糖尿病是包括脑卒中在内的心脑血管事件的主要危险因素。糖尿病可直接诱发或加重脑血管损伤，糖尿病患者急性脑梗死复发率较高，预后较差。目前，研究者认为炎症反应加剧、氧化应激增强及长期高血糖导致的血管壁损伤、血管硬化等是糖尿病脑梗死的独特病理生理机制，由此导致的神经功能损伤、预后不良等是临床上的主要难题。
汉黄芩素：是从黄芩根中提取的一种黄酮类化合物，具有抗炎、抗氧化和神经保护作用。既往研究发现，汉黄芩素对脑缺血再灌注损伤有保护作用，还能降低糖尿病小鼠的血糖及其并发症。

背景：汉黄芩素是黄芩根中提取的一种黄酮类化合物，既往研究表明汉黄芩素对脑缺血再灌注损伤有保护作用，还能降低糖尿病小鼠的血糖及其并发症，但其在糖尿病脑梗死中的作用及机制还不清楚。
目的：探究汉黄芩素对糖尿病脑梗死大鼠神经损伤的影响，并探究其作用机制。
方法：将SD大鼠随机分为6组：对照组、模型组、汉黄芩素低、中、高剂量组和汉黄芩素高剂量+RhoA激活剂组，每组10只。除对照组外，其余组通过腹腔注射链脲佐菌素和大脑中动脉闭塞法构建糖尿病脑梗死大鼠模型，汉黄芩素低、中、高剂量组分别灌胃10，20，40 mg/kg汉黄芩素，汉黄芩素高剂量+RhoA激活剂组灌胃40 mg/kg汉黄芩素并腹腔注射10 mg/kg溶血磷脂酸，对照组和模型组给予等量生理盐水，1次/d，连续7 d。末次给药结束后，各组大鼠进行神经功能缺损评分，检测血糖水平，TTC染色检测脑梗死体积，苏木精-伊红染色观察脑组织病理变化，ELISA试剂盒检测脑组织中肿瘤坏死因子α、白细胞介素6和丙二醛、超氧化物歧化酶水平，Western blot检测脑组织中RhoA、ROCK2蛋白表达。
结果与结论：①与对照组相比，模型组大鼠神经元结构严重受损，细胞坏死、变性；神经功能缺损评分、血糖水平、脑梗死体积升高(P < 0.05)；脑组织中肿瘤坏死因子α、白细胞介素6、丙二醛水平升高(P < 0.05)，超氧化物歧化酶水平下降(P < 0.05)；脑组织中RhoA、ROCK2蛋白表达升高(P < 0.05)；②与模型组相比，汉黄芩素低、中、高剂量组神经元损伤改善，细胞变性和坏死减少；神经功能缺损评分、血糖水平、脑梗死体积下降(P < 0.05)；脑组织中肿瘤坏死因子α、白细胞介素6、丙二醛水平下降(P < 0.05)，超氧化物歧化酶水平升高(P < 0.05)；脑组织中RhoA、ROCK2蛋白表达下降(P < 0.05)；③与汉黄芩素高剂量组相比，汉黄芩素高剂量+RhoA激活剂组明显抑制糖尿病脑梗死大鼠上述指标的改善(P < 0.05)。结果表明：汉黄芩素能够改善糖尿病脑梗死大鼠血糖水平，减轻脑梗死和神经损伤，其作用机制可能与抑制RhoA/ROCK信号通路有关。
https://orcid.org/0009-0008-8034-8651(王欢欢)

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: 糖尿病, 脑梗死, 神经损伤, 汉黄芩素, Ras同源基因家族成员A, Rho相关卷曲螺旋蛋白激酶

Abstract: BACKGROUND: Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis. Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury, and can also reduce blood sugar and complications in diabetic mice, but its role and mechanism in diabetic cerebral infarction remain unclear.
OBJECTIVE: To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. 
METHODS: Sprague-Dawley rats were randomly divided into six groups: control group, model group, low-dose wogonin group, medium-dose wogonin group, high-dose wogonin group, and high-dose wogonin+ Ras homolog gene family member A (RhoA) activator group. Except for the control group, the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion. Low, medium- and high-dose wogonin groups were intragastrically given 10, 20, 40 mg/kg wogonin, respectively; high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid; control group and model group were given the same amount of normal saline once a day for 7 consecutive days. Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose. TTC staining was applied to detect the volume of cerebral infarction. Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue. ELISA kit was applied to detect tumor necrosis factor-α, interleukin-6, malondialdehyde, and superoxide dismutase levels in brain tissue. Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase (ROCK) 2 in brain tissue. 
RESULTS AND CONCLUSION: Compared with the control group, the neuronal structure of rats in the model group was severely damaged, with cell necrosis and degeneration, the neurological deficit score, blood glucose level, and infarct volume were significantly elevated (P < 0.05), the levels of tumor necrosis factor-α, interleukin-6, and malondialdehyde, and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased (P < 0.05), and the superoxide dismutase level was decreased (P < 0.05). Compared with the model group, the low-, medium-, and high-dose wogonin groups showed improved neuronal damage, reduced cell degeneration and necrosis, a significant reduction in neurological deficit score, blood glucose level, infarct volume, and the levels of tumor necrosis factor-α, interleukin-6, and malondialdehyde, and the protein expression of RhoA and ROCK2 in brain tissue, and an increase in the superoxide dismutase level (P < 0.05). Compared with the high-dose wogonin group, the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction (P < 0.05). To conclude, wogonin can improve the blood glucose level in rats with diabetic cerebral infarction, reduce cerebral infarction and nerve injury, and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

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

Key words: diabetes mellitus, cerebral infarction, nerve injury, wogonin, Ras homolog gene family member A, Rho-associated protein kinase

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