Effects Of Vinpocetine On The Expression Of NF-κ B And Density Of MMP-9after Focal Cerebral Ischemia/Reperfusion

ObjectiveTo investigate the levels of Matrix metalloproteinase-9(MMP-9) and the nuclear transcription factor (NF-KB) in serum at different time points after vinpocetine intervention in cerebral ischemia-reperfusion injury and to find the role of vinpocetine in inflammation of ischemia-reperfusion injury and apoptosis mechanism after acute cerebral infarction and to explore the clinical value of vinpocetine in the future.MethodsSixty patients within6-12hours of acute cerebral infarction and thirty healthy volunteers were recruited.All patients were randomly divided into treatment group and Vinpocetine intervention group. There were28patients,13males and15females, aged42to77years, mean age64.8+10.5years old in former group and32patients,18males and14females, aged48to80years, mean age67.3±10.5years old in the latter. Conventional therapy (anti-platelet aggregation, lipid-lowering and plaque stabilization, improving circulation and other treatment) were used in treatment control group, and intravenous vinpocetine300mg every day besides in vinpocetine intervention group. The DWI sequence of MRI were received within1-2days after admitting, and fasting venous blood were collected before treatment, the first24h and72h after treatment. Fasting venous blood samples were collected in health control group. Double antibody sandwich ELISA assay were used to evaluate MMP-9, and flow cytometry were used to measure NF-KB expression of mononuclear cells in peripheral blood. SPSS17.0software package was used to analyze the results.Results1. The levels of MMP-9and NF-KB expression were significantly higher in patient group than in HC group. The levels of MMP-9and NF-KB expression were significantly different in treatment group and Vinpocetine intervention group before or24h and72h after treatment (P<0.05). The levels of MMP-9and NF-KB expression were significantly different before or after treatment in both groups (P<0.05) 2. The levels of MMP-9and NF-KB expression were significantly higher in large volume subgroup of cerebral infarction than in middle volume subgroup (P<0.05).The levels were significantly higher in middle volume subgroup than the small volume subgroup (P<0.05).The linear correlation analysis showed that there was no significant correlation between the volume of cerebral infarction and NF-KB expression (r=0.42,P>0.05), but significant correlation was found between the volume and MMP-9level (1=0.69, P<0.05). In all subgroups, the levels of MMP-9and NF-KB expression were significantly different before and after treatment (P<0.05)3. Evaluation of NF-kB expression:Flow cytometry were used to measure NF-KB expression of mononuclear cells in peripheral blood. The levels of NF-KB expression24h after treatment were significantly higher than before in both treatment group and Vinpocetine intervention group (P<0.05). The decreasing degrees of NF-KB expression48h after treatment were significantly different in treatment group and Vinpocetine intervention group (P<0.05). NF-KB expressions of24h and72h after treatment were both significantly different in treatment group when compared to Vinpocetine intervention group (P<0.05). The level of P65expression of NF-kB24h after treatment reached its peak and was significantly higher than before and72h after treatment (P<0.05), and it still maintained at a high level72h after treatment, but lower than24h.4.Serum concentrations of MMP-9:The concentrations of MMP-924h after treatment were significantly higher than before treatment in both vinpocetine intervention group and treatment group (P<0.05). The decreasing degrees of concentration of MMP-948h after treatment were significantly different in both groups (P<0.05) Concentrations of MMP-9of24h and48h after treatment were both significantly different in treatment group when compared to Vinpocetine intervention group (P<0.05). Concentration of MMP-924h after treatment reached its peak and was significantly higher than before and72h after treatment (P<0.05), and it still maintained at a high level72h after treatment, but lower than24h.Conclusions1.After acute cerebral infarction, the expression activity of NF-KB and the concentration of MMP-9were significantly increased, which is considered to be related with immune and inflammatory responses and apoptosis induction.2. After treatment, the expression activity of NF-KB and the concentration of MMP-9reached peak and declined slowly, and it declined more rapidly in vinpocetine group, which inferred that vinpocetine may inhibit MMP-9by reducing NF-KB expression, and to inhibit inflammatory response and apoptosis pathway caused by NF-KB, MMP-9and other inflammation-induced cytokines in cerebral ischemia reperfusion injury, and play a role in brain protection by reducing inflammation and neuronal apoptosis.3. No significant correlation was observed between the volume of infarction and the expression activity of NF-KB. The volume of infarction showed positively correlation with MMP-9concentration, which suggests that MMP-9can be used as a predictor of infarction volume. After treatment of vinpocetine, both NF-Kb expression activity and MMP-9concentrations decreased in each subgroups, suggesting that vinpocetine inhibit inflammatory response and apoptosis pathway caused by NF-KB, MMP-9and other inflammation-induced cytokines in cerebral ischemia reperfusion injury, and play a role in brain protection by reducing inflammation and neuronal apoptosis, regardless of the volume of infarction.