RESUMEN
Methotrexate (MTX)has dual effects of anti-inflam-matory and immune suppression,and its pharmacological mecha-nism is complex,diverse and synergistic.This paper summari-zes the main anti-inflammatory mechanism of low-dose MTX,in-cluding inhibition of JAK/STAT pathway,inhibition of inflam-matory reaction and immune response,increasing the accumula-tion of adenosine and the function of intracellular metabolites (methotrexate polyglutamate).In addition,low-dose MTX can inhibit oxidation by decreasing the level of lipid peroxidation, suppress the inflammatory response to secondary spinal cord in-jury,reduce spinal cord ischemia reperfusion injury and neuro-pathic pain,thus playing a neuroprotective role by a series of pharmacological mechanism.The anti-inflammatory mechanism of low-dose MTX and its application in spinal cord injury were reviewed,to guide the further research on the anti-inflammatory effect of MTX,and provide a theoretical basis for new drugs for clinical treatment of spinal cord injury.
RESUMEN
OBJECTIVE:To investigate the protective effect and mechanism of Wei medicine Cichorium glandulosum 95% eth-anol extract(CG-I)on immunological liver injury in mice,and provide reference for post-screening its effective site. METHODS:60 mice were randomly divided into blank control group(normal saline),model group(normal saline),positive control group(Di-ammonium glycyrrhizinate,100 mg/kg) and CG-I high-dose,medium-dose,low-dose groups (calculated by crude drugs as 200, 100,50 g/kg),10 in each group,intragastrically administrated once every day,for 10 d. After 1 h of last administration,except for blank control group,mice in other groups were intravenously injected Con-A in tail to induce immunological liver injury. After 8 h of modeling,tumor necrosis factor α(TNF-α),interferon γ(IFN-γ),interleukin 1β(IL-1β)contents in serum were detected;liver and spleen indexes were calculated. The pathological changes in liver tissue were observed,and aspartate aminotransferase(AST), alanine aminotransferase (ALT), glutathione S-transferase (GST), alkaline phosphatase (AKP), total superoxide dismutase (T-SOD),malondialdehyde(MDA)levels in liver tissue were detected. RESULTS:Compared with blank control group,TNF-α, IFN-γ,IL-1β contents in serum in model group were significantly increased;liver,spleen indexes and AST,ALT,GST,AKP, T-SOD levels in liver tissue were significantly increased;and MDA level in liver tissue was significantly reduced,with statistical significances(P<0.05 or P<0.01);liver of mice in model group was cluttered,showing swelling,necrosis and other diseases in liver cells. Compared with model group, except that AST, ALT,AKP levels in liver tissue in CG-I low-dose group and MDA, IFN-γ contents in serum in CG-I medium-dose, low-dose groups had no significant decrease, other indexes were significantly improved (P<0.05 or P<0.01);and patho-logical changes in liver tissue were relieved to varying degrees. CONCLUSIONS:CG-I shows protective effect on Con-A-in-duced immunological liver injury in mice,especially the high dose and medium dose. The mechanism may be associated with its an-ti-oxidation and anti-inflammatory effects.