RESUMO
<p><b>OBJECTIVE</b>To study the molecular mechanism of Zuogui Pill (ZGP) and Yougui Pill (YGP) on axonal regeneration in rats with experimental autoimmune encephalomyelitis (EAE).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Assuntos
Animais , Masculino , Ratos , Axônios , Metabolismo , Patologia , Fisiologia , Encéfalo , Metabolismo , Patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas , Farmacologia , Encefalomielite Autoimune Experimental , Tratamento Farmacológico , Metabolismo , Patologia , Proteínas Ligadas por GPI , Proteínas da Mielina , Metabolismo , Fator de Crescimento Neural , Metabolismo , Regeneração Nervosa , Proteínas Nogo , Receptor Nogo 1 , Ratos Endogâmicos Lew , Receptores de Superfície Celular , Receptores de Peptídeos , Metabolismo , Pesquisa , Transdução de Sinais , ComprimidosRESUMO
AIM: To investigate the therapeutic effects of Lycium barbarum polysaccharide (LBP) on mitomycin C (MMC)-induced myelosuppressive mice. METHODS: Mice were intravenously injected with MMC 150 mg/kg for two consecutive days from day -1 to day 0 to produce severe myelosuppression, and then treated by s.c. injections of LBP (100 or 200 mg/kg/day) from days 0 to 6. Blood samples were collected from the tail veins of mice on days 7, 10, 12, 14, 17, 19, 21, 24 and 27, and peripheral white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB) and platelet counts (PLT) etc. were monitored. RESULTS: LBP at 100 mg/kg (LBP-L) on day 14 and LBP at 200 mg/kg (LBP-H) on days 10, 14, 17, 19 and 21, significantly ameliorated the decrease of peripheral RBC, HGB and hematocrit (HCT) of myelosuppressive mice compared to the control. LBP-L on days 12 and days 14 and LBP-H on days 10, 12, 14, 17, 19 and 21, significantly enhanced peripheral PLT recovery of myelosuppressive mice compared to the control. LBP-H on days 12, 17, 19 and 21, significantly inhibited the increase of mean platelet volume (MPV) of myelosuppressive mice compared to the control. LBP showed no obviously effect on neutropenia induced in mice by MMC. CONCLUSION: LBP is effective on peripheral RBC and PLT recovery of MMC-induced myelosuppressive mice.