Journal Article

Tanshinone IIA Promotes Axonal Regeneration in Rats with Focal Cerebral Ischemia Through the Inhibition of Nogo-A/NgR1/RhoA/ROCKII/MLC Signaling

Han, Ying, Liu, Yanming, Ni, Guangxiao, Wang, Yali, Jia, Lin, Wang, Jing

2020

Overview

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. 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. 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. 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.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove,Dove Medical Press
• Subject: Abietanes - chemistry / Abietanes - isolation & purification / Abietanes - pharmacology / Animal models / Animals / Anti-Inflammatory Agents, Non-Steroidal - chemistry / Anti-Inflammatory Agents, Non-Steroidal - isolation & purification / Anti-Inflammatory Agents, Non-Steroidal - pharmacology / axon regeneration / axonal regeneration / Axons - drug effects / Axons - metabolism / Brain Ischemia - drug therapy / Brain Ischemia - metabolism / Brain Ischemia - pathology / Carotid arteries / Cerebral infarction / Cerebral ischemia / Change detection / Disease Models, Animal / GAP-43 protein / Humans / Immunofluorescence / Infarction / Ischemia / Kinases / Laboratory animals / Medical research / Molecular Structure / Muscle proteins / Myosin / Myosin Light Chains - antagonists & inhibitors / Myosin Light Chains - metabolism / neurite outgrowth inhibitor-A / Neurofilaments / Neurons / Neurophysiology / Neuroprotection / neuroprotective effect / Nogo protein / Nogo Proteins - antagonists & inhibitors / Nogo Proteins - metabolism / Nogo receptor / Nogo Receptor 1 - antagonists & inhibitors / Nogo Receptor 1 - metabolism / Original Research / Protein kinase / Protein kinases / Proteins / Rats / Rats, Sprague-Dawley / Regeneration / rho GTP-Binding Proteins - antagonists & inhibitors / rho GTP-Binding Proteins - metabolism / rho-Associated Kinases / Rho-associated protein kinase / RhoA protein / Salvia miltiorrhiza - chemistry / Signal transduction / Signal Transduction - drug effects / Signaling / Staining / Stroke / Surgery / Survival / tanshinone IIA / Traditional Chinese medicine / Veins & arteries / Western blotting