Drug Design, Development and Therapy (Jul 2020)
Tanshinone IIA Promotes Axonal Regeneration in Rats with Focal Cerebral Ischemia Through the Inhibition of Nogo-A/NgR1/RhoA/ROCKII/MLC Signaling
Abstract
Jing Wang,1 Guangxiao Ni,2 Yanming Liu,3 Ying Han,4 Lin Jia,5 Yali Wang1,6 1Department of Chinese Medicine Diagnostics, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, People’s Republic of China; 2Department of Rehabilitation Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, People’s Republic of China; 3College of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, People’s Republic of China; 4Department of Chinese Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, People’s Republic of China; 5Department of Respiratory Diseases, Hebei Province Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei 050000, People’s Republic of China; 6College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, People’s Republic of ChinaCorrespondence: Yali WangDepartment of Chinese Medicine Diagnostics, Hebei University of Chinese Medicine, Luquan Xingyuan Road 3, Shijiazhuang, Hebei 050200, People’s Republic of ChinaEmail [email protected]: The aim of this study was to evaluate the neuroprotective effect of tanshinone IIA (TSA) on focal cerebral ischemia in rats and to investigate whether it was associated with Nogo-A/NgR1/RhoA/Rho-associated protein kinase 2 (ROCKII)/myosin light chain (MLC) signaling.Methods: In this study, focal cerebral ischemia animal model was used. Neurological deficit scores and infarction volume were investigated to evaluate the neuroprotection of TSA. Hematoxylin-eosin staining, Nissl staining, and immunofluorescence staining were conducted to detect ischemic changes in brain tissue and changes in neurofilament protein 200 (NF200) and growth-associated protein-43 (GAP-43) expression, respectively. Western blotting and qRT-PCR analyses were used to detect the expression levels of NF200, GAP-43 and Nogo-A/NgR1/RhoA/ROCKII/MLC pathway-related signaling molecules.Results: TSA treatment can improve the survival rate of rats, reduce the neurological score and infarct volume, and reduce neuron damage. In addition, TSA also increased axon length and enhanced expression of NF200 and GAP-43. Importantly, TSA significantly attenuated the expression of Nogo-A, NgR1, RhoA, ROCKII, and p-MLC, and thus inhibiting the activation of this signaling pathway.Conclusion: TSA promoted axonal regeneration by inhibiting the Nogo-A/NgR1/RhoA/ROCKII/MLC signaling pathway, thereby exerting neuroprotective effects in cerebral ischemia rats, which provided support for the clinical application of TSA in stroke treatment.Keywords: tanshinone IIA, cerebral ischemia, axonal regeneration, neuroprotective effect, neurite outgrowth inhibitor-A, Nogo receptor, Rho-associated protein kinase
