Tang Qiang, Ye Tao, Liang Runyu, Wang Yan, Li Hongyu, Zhang Jiyao, Yuan Xingxing, Zhu Luwen
The Second Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Evid Based Complement Alternat Med. 2021 Nov 12;2021:1418616. doi: 10.1155/2021/1418616. eCollection 2021.
Stroke is the leading cause of long-term disability in developed countries. Multitudinous evidence suggests that treadmill training treatment is beneficial for balance and stroke rehabilitation; however, the need for stroke therapy remains unmet. In the present study, a cerebral ischemia rat model was established by permanent middle cerebral artery occlusion (pMCAO) to explore the therapeutic effect and mechanism of scalp acupuncture combined with treadmill training on ischemic stroke. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and neuronal nuclear protein (NeuN) double staining and cellular inhibitor of apoptosis protein-1 (cIAP1) and NeuN immunofluorescence double staining were used to detect the short-term and long-term neuroprotective effects of scalp acupuncture combined with treadmill training on pMCAO rats. In addition, the antiapoptotic effect of the combined treatment was evaluated in pMCAO rats transfected with cIAP1 shRNA. Western blotting was used to detect the relative protein expression in the caspase-8/-9/-3 activation pathway downstream of cIAP1 to further clarify its regulatory mechanism. Our results showed that scalp acupuncture combined with treadmill training successfully achieved short-term and long-term functional improvement within 14 days after stroke, significantly inhibited neuronal apoptosis, and upregulated the expression of cIAP1 protein in the ischemic penumbra area of the ischemic brain. However, no significant functional improvement and antiapoptotic effect were found in pMCAO rats transfected with cIAP1 shRNA. Western blotting results showed that the combined therapy markedly inhibited the activation of the caspase-8/-9/-3 pathway. These findings indicate that scalp acupuncture combined with treadmill training therapy may serve as a more effective alternative modality in the treatment of ischemic stroke, playing an antiapoptotic role by upregulating the expression of cIAP1 and inhibiting the activation of the caspase-8/-9/-3 pathway.
中风是发达国家长期残疾的主要原因。大量证据表明，跑步机训练疗法对平衡和中风康复有益；然而，中风治疗的需求仍未得到满足。在本研究中，通过永久性大脑中动脉闭塞（pMCAO）建立脑缺血大鼠模型，以探讨头皮针结合跑步机训练对缺血性中风的治疗效果及机制。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法与神经元核蛋白（NeuN）双重染色以及细胞凋亡抑制蛋白-1（cIAP1）与NeuN免疫荧光双重染色，检测头皮针结合跑步机训练对pMCAO大鼠的短期和长期神经保护作用。此外，在转染cIAP1 shRNA的pMCAO大鼠中评估联合治疗的抗凋亡作用。采用蛋白质印迹法检测cIAP1下游半胱天冬酶-8/-9/-3激活途径中的相关蛋白表达，以进一步阐明其调控机制。我们的结果表明，头皮针结合跑步机训练在中风后14天内成功实现了短期和长期功能改善，显著抑制了神经元凋亡，并上调了缺血性脑缺血半暗带区域cIAP1蛋白的表达。然而，在转染cIAP1 shRNA的pMCAO大鼠中未发现明显的功能改善和抗凋亡作用。蛋白质印迹结果显示，联合治疗显著抑制了半胱天冬酶-8/-9/-3途径的激活。这些发现表明，头皮针结合跑步机训练疗法可能是治疗缺血性中风更有效的替代方式，通过上调cIAP1的表达并抑制半胱天冬酶-8/-9/-3途径的激活发挥抗凋亡作用。
