切换至 "中华医学电子期刊资源库"

中华脑科疾病与康复杂志(电子版) ›› 2025, Vol. 15 ›› Issue (05) : 261 -267. doi: 10.3877/cma.j.issn.2095-123X.2025.05.002

基础研究

基于HIF-1α/VEGF通路探讨经颅交流电刺激联合运动训练对脑梗死后肢体痉挛大鼠功能恢复的影响与机制研究
李小萍, 张清芳, 李东霞, 陈文生, 王坤, 王诚婷, 龙建军()   
  1. 518035 深圳市第二人民医院康复医学科
  • 收稿日期:2024-12-10 出版日期:2025-10-15
  • 通信作者: 龙建军

Effect and mechanism of transcranial alternating current stimulation combined with exercise training on the functional recovery of rats with limb spasm after cerebral infarction based on the HIF-1α/VEGF pathway

Xiaoping Li, Qingfang Zhang, Dongxia Li, Wensheng Chen, Kun Wang, Chengting Wang, Jianjun Long()   

  1. Department of Rehabilitation Medicine, Shenzhen Second People's Hospital, Shenzhen 518035, China
  • Received:2024-12-10 Published:2025-10-15
  • Corresponding author: Jianjun Long
  • Supported by:
    Guangdong Medical Science and Technology Research Fund(A2021169); "Li Jian'an Team of Nanjing Medical University" Funded Project of Shenzhen Three Elites Project(SZSM202111010)
引用本文:

李小萍, 张清芳, 李东霞, 陈文生, 王坤, 王诚婷, 龙建军. 基于HIF-1α/VEGF通路探讨经颅交流电刺激联合运动训练对脑梗死后肢体痉挛大鼠功能恢复的影响与机制研究[J/OL]. 中华脑科疾病与康复杂志(电子版), 2025, 15(05): 261-267.

Xiaoping Li, Qingfang Zhang, Dongxia Li, Wensheng Chen, Kun Wang, Chengting Wang, Jianjun Long. Effect and mechanism of transcranial alternating current stimulation combined with exercise training on the functional recovery of rats with limb spasm after cerebral infarction based on the HIF-1α/VEGF pathway[J/OL]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2025, 15(05): 261-267.

目的

基于低氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)通路分析经颅交流电刺激联合运动训练对脑梗死后肢体痉挛大鼠功能恢复的影响。

方法

50只SPF级SD雄性大鼠中采用随机数字表法选取10只大鼠作为正常(NO)组,余40只采用线栓法联合内囊注射N-甲基-D-天冬氨酸制备脑梗死后肢体痉挛大鼠模型,其中30只制备成功。采用随机数字表法将模型大鼠分为模型(MO)组、联合(UN)组、联合+HIF-1α/VEGF通路抑制剂(UH)组,每组10只。UN组给予经颅交流电刺激联合运动训练干预,UH组在UN组基础上腹腔注射HIF-1α/VEGF通路抑制剂16 mg/kg,NO组、MO组不予治疗。治疗结束后,采用Zea-Longa评分、改良Ashworth评分、Feeney平衡试验、网屏试验评估功能恢复情况,HE染色检测脑组织病理形态,RT-PCR及Western blot检测脑组织HIF-1α/VEGF通路表达情况。

结果

4组大鼠干预后的Zea-Longa评分、改良Ashworth评分、Feeney平衡试验评分及网屏试验评分比较,差异均有统计学意义(P<0.05),且NO组<UN组<UH组<MO组,组间两两比较差异均有统计学意义(P<0.05)。HE染色结果显示,NO组脑组织结构完整,神经细胞分布均匀;MO组脑组织结构遭到破坏,可见脑组织水肿,神经细胞分布紊乱,细胞核萎缩;病理结构改善情况:UN组>UH组>MO组。4组大鼠的脑组织HIF-1α和VEGF mRNA及蛋白表达比较,差异均有统计学意义(P<0.05);脑组织HIF-1α/VEGF mRNA表达水平比较,MO组<NO组<UH组<UN组,两两比较差异均有统计学意义(P<0.05);HIF-1α、VEGF蛋白表达水平比较,MO组<UH组<UN组<NO组,两两比较差异均有统计学意义(P<0.05)。

结论

经颅交流电刺激联合运动训练对脑梗死后肢体痉挛大鼠功能恢复具有显著疗效,可有效改善大鼠的神经功能及肢体功能,这可能与调控HIF-1α/VEGF通路有关。

Objective

To explore the effect of transcranial alternating current stimulation combined with exercise training on functional recovery in rats with limb spasm after cerebral infarction based on hypoxic inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway.

Methods

Out of 50 SPF grade SD male rats, 10 rats were selected as the normal (NO) group using a random number table method, while the remaining 40 rats were used to establish rat models of limb spasm after cerebral infarction by suture method combined with internal capsule injection of N-methyl-D-aspartic acid. Among them, 30 rats were successfully prepared. The model rats were randomly divided into a normal (NO) group, a model (MO) group, a combined (UN) group, and a combined+HIF-1α/VEGF pathway inhibitor (UH) group using a random number table method, with 10 rats in each group. The UN group received transcranial alternating current stimulation combined with exercise training intervention, while the UH group received intraperitoneal injection of HIF-1α/VEGF pathway inhibitor at a dose of 16 mg/kg on top of the UN group. The NO group and MO group did not receive treatment. After the treatment, Zea-Longa score, modified Ashworth score, Feeney balance test, and screen test were used to evaluate functional recovery. HE staining was used to detect the pathological morphology of brain tissue, and RT-PCR and immunoblotting were used to detect the expression of HIF-1α/VEGF pathway in brain tissue.

Results

The Zea-Longa score, modified Ashworth score, Feeney balance test score and screen test score were compared among the four groups of rats after intervention, and the differences were statistically significant (P<0.05); Moreover, the NO group<UN group<UH group<MO group, and the differences of pairwise comparison among four groups were statistically significant (P<0.05). The HE staining results showed that, the brain tissue structure of the NO group is intact, and the distribution of nerve cells is uniform; The brain tissue structure of the MO group was damaged, showing edema of the brain tissue, disordered distribution of nerve cells, and nuclear atrophy; Improvement of pathological structure: UN group>UH group>MO group. The mRNA and protein expression of HIF-1α and VEGF in the brain tissues of four groups of rats were compared, and the differences were statistically significant (P<0.05); The expression levels of HIF-1α/VEGF mRNA in brain tissue were compared, with MO group<NO group<UH group<UN group, and the differences of pairwise comparison among four groups were statistically significant (P<0.05); The expression levels of HIF-1α and VEGF proteins were compared, with MO group<UH group<UN group<NO group, and the differences of pairwise comparison among four groups were statistically significant (P<0.05).

Conclusions

Transcranial AC stimulation combined with exercise training has a significant effect on the functional recovery of rats with limb spasm after cerebral infarction, and can effectively improve the nerve function and limb function of rats, which may be related to the regulation of HIF-1α/VEGF pathway.

表1 4组大鼠干预后神经功能及肌张力比较(分,mean±SD)
Tab.1 Comparison of neurological function and muscle tone after intervention in 4 groups of rats (score, mean±SD)
表2 4组大鼠干预后的运动功能比较(分,mean±SD)
Tab.2 Comparison of motor function after intervention in 4 groups of rats (score, mean±SD)
图1 4组大鼠干预后的脑组织病理形态(HE染色,×400)A:NO组;B:MO组;C:UN组;D:UH组
Fig.1 Pathological morphology of rat brain tissues after intervention in the 4 groups of rats (HE staining, ×400)
表3 4组大鼠干预后脑组织HIF-1α/VEGF mRNA表达水平比较(mean±SD
Tab.3 Comparison of the expression levels of HIF-1α/VEGF mRNA in brain tissues after intervention in 4 groups of rats (mean±SD)
图2 4组大鼠干预后的脑组织HIF-1α/VEGF蛋白表达Western blot检测结果HIF-1α:低氧诱导因子-1α;VEGF:血管内皮生长因子;GAPDH:甘油醛-3-磷酸脱氢酶
Fig.2 Western blot detection results of HIF-1α/VEGF protein expression in brain tissue after intervention in 4 groups of rats
表4 4组大鼠干预后脑组织HIF-1α/VEGF蛋白表达水平比较(mean±SD
Tab.4 Comparison of HIF-1α/VEGF protein expression levels in brain tissues after intervention in 4 groups of rats (mean±SD)
[1]
王旭霞,盛超,孙洁,等.探究化痰通络汤加减联合康复训练对急性脑梗死后吞咽障碍(痰瘀互结证)的治疗效果[J].中华脑科疾病与康复杂志(电子版), 2021, 11(5): 294-299. DOI: 10.3877/cma.j.issn.2095-123X.2021.05.008.
[2]
Govardhan C, Rn P, D'Souza F. Cerebral infarction following a wasp sting[J]. Indian J Pediatr, 2024, 91(9): 974-975. DOI: 10.1007/s12098-023-04908-y.
[3]
岳亚男,郑晨晨,马勇,等.椎针通督循经疗法联合通经解痉汤治疗脑梗死后肢体痉挛临床研究[J].新中医, 2024, 56(9): 186-190. DOI: 10.13457/j.cnki.jncm.2024.09.037.
[4]
Song Y, Liu F, Kang L, et al. Effects of transcranial direct current stimulation on graph naming function and brain connectivity in postinfarction aphasia patients: an fMRI study[J]. Folia Phoniatr Logop, 2024, 76(3): 264-272. DOI: 10.1159/000534188.
[5]
Chen S, Huang J, Tang X, et al. Effects of transient electrical acupuncture stimulation combined with rehabilitation training on hemorheology, neurological function and BDNF in patients with cerebral infarction[J]. Front Surg, 2022, 9: 839523. DOI: 10.3389/fsurg.2022.839523.
[6]
Zhou P, Yu S, Wang X, et al. Ferulic acid methyl ester attenuates cerebral ischemia-reperfusion injury in rats by modulating PI3K/HIF-1α/VEGF signaling pathway[J]. J Inflamm Res, 2024, 17: 5741-5762. DOI: 10.2147/jir.S473665.
[7]
Liu X, Sui X, Zhang Y, et al. Efficacy of puerarin in rats with focal cerebral ischemia through modulation of the SIRT1/HIF-1α/VEGF signaling pathway and its effect on synaptic plasticity[J]. Heliyon, 2023, 9(5): e15872. DOI: 10.1016/j.heliyon.2023.e15872.
[8]
Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91. DOI: 10.1161/01.str.20.1.84.
[9]
Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity[J]. Phys Ther, 1987, 67(2): 206-207. DOI: 10.1093/ptj/67.2.206.
[10]
张建云,梅紧紧,张帅迪,等.基于谷胱甘肽抗氧化系统探讨督脉电针对脑卒中后肢体痉挛大鼠氧化应激的影响[J].北京中医药大学学报, 2024, 47(1): 124-132. DOI: 10.3969/j.issn.1006-2157.2024.01.017.
[11]
孙玮辰. "通经调形"推拿法治疗早期中风后肢体痉挛的临床疗效及效应机制研究[D].长春:长春中医药大学, 2023.
[12]
Kong X, Lyu W, Lin X, et al. Transcranial direct current stimulation enhances the protective effect of isoflurane preconditioning on cerebral ischemia/reperfusion injury: a new mechanism associated with the nuclear protein Akirin2[J]. CNS Neurosci Ther, 2024, 30(9): e70033. DOI: 10.1111/cns.70033.
[13]
Wei J, Zhu X, Xia L, et al. Intermittent pneumatic compression combined with rehabilitation training improves motor function deficits in patients with acute cerebral infarction[J]. Acta Neurol Belg, 2021, 121(6): 1561-1566. DOI: 10.1007/s13760-020-01414-2.
[14]
绽晟,黄麟荇,易丽贞,等.电针患侧曲池、阳陵泉穴对脑梗死后肢体痉挛大鼠的影响与机制研究[J].康复学报, 2024, 34(2): 133-139. DOI: 10.3724/SP.J.1329.2024.02006.
[15]
李明哲,张英杰,单春雷.电针结合经颅交流电刺激对脑缺血大鼠神经炎症和凋亡相关基因表达的影响[J].中国康复医学杂志, 2024, 39(2): 163-169. DOI: 10.3969/j.issn.1001-1242.2024.02.003.
[16]
于晓岚,谭香芹,刘欣.重复经颅磁刺激联合康复训练治疗脑梗死后肢体运动障碍的临床疗效[J].当代医学, 2023, 29(19): 9-13.
[17]
Chen X, Qian W, Zhang Y, et al. Ginsenoside CK cooperates with bone mesenchymal stem cells to enhance angiogenesis post-stroke via GLUT1 and HIF-1α/VEGF pathway[J]. Phytother Res, 2024, 38(8): 4321-4335. DOI: 10.1002/ptr.8235.
[18]
余秀,涂星,陈嘉碧,等.基于HIF-1α/VEGF通路探讨土家族麝针疗法"活血生新"干预缺血性脑卒中大鼠的作用机制[J].中国老年学杂志, 2024, 44(7): 1722-1725. DOI: 10.3969/j.issn.1005-9202.2024.07.044.
[19]
邹正,付丽丽,费爽,等.远隔缺血预适应通过激活HIF-1α/VEGF通路保护大鼠缺血性脑卒中[J].神经解剖学杂志, 2023, 39(3): 341-345. DOI: 10.16557/j.cnki.1000-7547.2023.03.014.
[20]
徐浩,沈剑,赵昱,等.电针预处理大鼠百会穴对脑缺血保护作用及HIF-1α相关机制的研究[J].神经解剖学杂志, 2015, 31(5): 617-622. DOI: 10.16557/1000-7547.2015050015.
[1] 丁河南, 林少强, 张杰龙, 赖世芳, 肖志满. 小剂量丙泊酚在肩关节脱位手法复位中的临床应用[J/OL]. 中华关节外科杂志(电子版), 2025, 19(04): 494-498.
[2] 罗鸣, 袁志, 樊俊俊, 廖炳辉, 党海峰, 郑天雷, 白灵心. 关节镜辅助经皮微创钢板内固定治疗胫骨平台骨折[J/OL]. 中华关节外科杂志(电子版), 2025, 19(01): 46-54.
[3] 董红华, 郭艮春, 江磊, 吴雪飞, 马飞翔, 李海凤. 骨科康复一体化模式在踝关节骨折快速康复中的应用[J/OL]. 中华关节外科杂志(电子版), 2023, 17(06): 802-807.
[4] 李越, 田润, 杨佩, 王坤正. 活动平台膝关节单髁置换术后蹲起活动的运动生物力学[J/OL]. 中华关节外科杂志(电子版), 2021, 15(05): 533-539.
[5] 柳宁强, 梁钰琪, 王聪, 穆生瑞, 解桐, 郭崇军, 牛东生. 不同间隔时间对分期双侧全膝关节置换术的影响[J/OL]. 中华关节外科杂志(电子版), 2021, 15(03): 345-349.
[6] 汤文倩, 徐向阳, 王松, 刘淑华. 运动康复在严重烧伤中的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2023, 18(02): 169-173.
[7] 刘军, 沈雯, 田小红, 周黎阳, 张丽, 郭慧, 张亚娟. COPD患者肺康复运动训练联合支气管扩张剂治疗的疗效分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(01): 107-110.
[8] 赵珞, 李伟, 任逸众, 张圆, 王敬钧, 贾岩波. 肩袖损伤中脂肪浸润的研究进展[J/OL]. 中华肩肘外科电子杂志, 2025, 13(02): 112-117.
[9] 郭丹. 肩周肌群的抗阻力量训练对肩袖损伤患者术后功能恢复及预后质量的影响[J/OL]. 中华肩肘外科电子杂志, 2024, 12(02): 115-120.
[10] 耿一博, 刘一齐, 刘小莉, 汪阳, 顾征, 宋英伦, 李涛, 李彤, 谭可, 王雁, 杨云娜, 李锦平. 原发性脑干出血患者预后危险因素分析[J/OL]. 中华神经创伤外科电子杂志, 2023, 09(02): 85-90.
[11] 鲁宁, 魏立友, 李亮, 张玉龙. 老年桡骨远端骨折小夹板治疗后早期腕关节功能恢复的相关因素分析[J/OL]. 中华老年骨科与康复电子杂志, 2024, 10(04): 222-228.
[12] 于敏. Bobath技术联合悬吊运动训练治疗痉挛性脑瘫患儿的效果研究[J/OL]. 中华脑科疾病与康复杂志(电子版), 2023, 13(01): 39-43.
[13] 姚晶, 邵兴慧. 射血分数中间值的心力衰竭患者的心脏康复研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(10): 961-964.
[14] 黄洪, 胡蓉, 吴友飞, 杨谨竹. 针灸联合下肢智能运动训练系统对脑梗死后偏瘫患者下肢运动功能和神经功能的影响[J/OL]. 中华临床医师杂志(电子版), 2021, 15(12): 933-936.
[15] 赵传, 姜鲁宁, 李岷, 李钊, 徐芳, 高雅文, 李鑫. 晚期非小细胞肺癌诊断及呼吸康复治疗的研究进展[J/OL]. 中华诊断学电子杂志, 2021, 09(03): 211-216.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?