Research on the mechanism of Zuogui Pill and Yougui Pill in promoting axonal regeneration in model rats of autoimmune encephalomyelitis.
OBJECTIVE
To study the molecular mechanism of Zuogui Pill (ZGP) and Yougui Pill (YGP) on axonal regeneration in rats with experimental autoimmune encephalomyelitis (EAE).


METHODS
EAE rat model was established by bilateral rear pedes subcutaneous injection of antigen made by mixing myelin basic protein (MBP) and complete Freud's adjuvant (CFA) in the volume ratio of 1:1. The pathological changes of axonal injury and regeneration in the brain and the spinal cord were observed on the 14th (the acute stage) and the 28th day (the remission stage) after modeling, with hematoxylin-eosin (HE) staining, silver stain, and immunohistochemical staining. The rats treated with prednisone acetate were taken as controls.


RESULTS
Observation under the light microscope with HE staining showed a sleeve-like change in rats' cerebrospinal parenchyma with inflammatory cell infiltration around the small vessels and neuronic denaturation, while silver staining showed excessive tumefaction and abscission of axon, and immunohistochemical analysis showed decreasing of nerve growth factor (NGF) expression at the acute stage of EAE, which was even more remarkable at the remission stage, showing significant difference as compared with the normal control (P<0.05). And the expressions of Nogo A, an axon growth inhibitor, and its receptor (Nogo-66 receptor, Ng R) were significantly higher than those in the normal control at the acute stage (P<0.01). However, after the intervention of ZGP and YGP, the pathological changes and axon damage in rats' brain and spinal cord were much more alleviated, and the NGF expression was significantly higher than that in the model group at the acute stage (P<0.05). The expression of NGF was even stronger during the remission stage, and a better effect was shown by YGP. As for Nogo A and Ng R expressions, they were significantly lower than those in the model group at the acute stage (P<0.05), but a better effect was shown by ZGP.


CONCLUSIONS
ZGP and YGP can prevent axonal injury and promote the axonal regeneration in rats of EAE, and the possible mechanism is to increase the expression of NGF and reduce the expression of Nogo A and its receptor. However, some differences are observed between the two Chinese preparations in their acting times and points, which provides a certain basis for revealing the modern connotation of the Chinese medicine theory on tonifying Shen ()-yin and Shen-yang.
Wang
Lei
L
School of Traditional Chinese Medicine, Capital Medical University, Beijing (100069), China. tmwangl@ccmu.edu.cn
Zhao
Hui
H
Fan
Yong-ping
YP
Gong
Hai-yang
HY
Li
Ming
M
Qi
Fang
F
Liu
Yan
Y
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058851:GPI-Linked Proteins; D008297:Male; D009185:Myelin Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D051381:Rats; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000378:metabolism; D012106:Research; D015398:Signal Transduction / Q000187:drug effects; D013607:Tablets
D004365:Drugs, Chinese Herbal; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat; D013607:Tablets; C552041:yougui; C552040:zuogui; D020932:Nerve Growth Factor
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