摘要
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-1αand 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-1αand 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.
作者
李小萍
张清芳
李东霞
陈文生
王坤
王诚婷
龙建军
Li Xiaoping;Zhang Qingfang;Li Dongxia;Chen Wensheng;Wang Kun;Wang Chengting;Long Jianjun(Department of Rehabilitation Medicine,Shenzhen Second People's Hospital,Shenzhen 518035,China)
出处
《中华脑科疾病与康复杂志(电子版)》
2025年第5期261-267,共7页
Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition)
基金
广东省医学科学技术研究基金(A2021169)
深圳市三名工程“南京医科大学励建安团队”资助项目(SZSM202111010)
关键词
经颅交流电刺激
运动训练
脑梗死后肢体痉挛
功能恢复
HIF-1α/VEGF通路
Transcranial alternating current stimulation
Sports training
Limb spasm after cerebral infarction
Functional recovery
HIF-1α/VEGF pathway
