| Objective: To explore the mechanism of effect of Modified Wendan Decoction(MWD)in treating AD with "Cerebrospinal Fluid Pharmacology in Chinese MateriaMedica".Methods: NG108-15 cells were cultured in vitro at 37℃in a humidified atmospherecontaining 5％CO2. Aβ25～35 fragment was dissolved with deionized distilledwater and aged for 4 days at 37℃. The cells were exposured to 5μmol/LAβ25～35 for 24h to establish the cell model. Twelve rabbits were divided intotwo groups at random, and garaged with MWD or physiological saline controlrespectively for 7 days to collect two kinds of cerebrospinal fluid(CSF), theyare CSF from rabbits treated with MWD and CSF from rabbits treated withphysiological saline. The cells were divided into six groups. The blank controlgroup was treated with blank CSE The low dose, middle dose, high dosegroups were treated with 5,10,20 percent of CSF from rabbits treated withModified Wendan Decoction for 24h respectively. The inhibitor of JNK(SP600125) group was treated with 25μmol/L SP600125 for 30 minutes toinhibit the JNK signal pathway before Aβ25～35 treatment.Test the expression ofp-JNK and p53 protein with immuocytochemistry and cell cycle with flowcytometry.Results: Both of p-JNK and p53 are obviously up-regulated in the model group anddose-dependently down-regulated after treated. The high dose group hassignificant difference with the SP600125 group and extremly significantdifference with the blank and the model group (P＜0.01). In addition to themodle group, the cells in G2/M phase are increased in different extent in allgroups, which means that the cells are arrested in S phase.Conclusion: The JNK signal pathway involve in cell apoptosis process induced by theAβ25～35 fragment, MWD cerebrospinal fluid can down-regulate the level ofp-JNK and p53, promote cells transfering from S phase to G2 phase. It canneutrolize the cytotoxicity in some degree. The possible mechanism is relevantto the activation of JNK signal pathway and down-regulation of p53. |
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