| Objective: To explore the action mechanism of MIF in complex regional pain syndrome type 1 and the possible mechanism of resveratrol in treatment of CRPS1,and compare the therapeutic efficacy in different doses of resveratrol to CRPS1.Methods: Part I:50 adult male SD rats were randomly divided into 7 groups:normal control group(n=5), sham-operated group(n=5), block-treated group-1(n=8),block-treated group-2(n=8), block-treated group-3(n=8), resveratrol-treated group(n=8), model control group(n=8). Block-treated group-1,2,3 were respectively given anti-CD74 antibodies[1mg/(kg·d)], PD98059[10mg/(kg·d)] and SB203580[10ug/(kg·d)]. Resveratrol-treated group was given resveratrol[20mg/(kg·d)]. Normal control group, sham-operated group and model control group were given 5% DMSO.All of the groups were continuously intraperitoneal injected for 14 days. Compared the pain behavior in rats, the MIF and TNF-α levels in serum before and after treatment(7days, 14days). The expressions of p38 MAPK and p-p38 MAPK in sciatic nerve of rats were detected by western blot after treatment. Part II:50 SD rats were randomly divided into 7 groups: normal control group(n=5), sham-operated group(n=5), targeted therapy group-1(n=8), targeted therapy group-2(n=8),resveratrol-treated group-1(n=8), resveratrol-treated group-2(n=8), model control group(n=8). Targeted therapy group-1,2 were respectively given ISO-1( MIF inhibitor) in doses of 0.1mg/(kg·d) and 1mg/(kg·d). Resveratrol-treated group-1,2were respectively given resveratrol in doses of 20mg/(kg·d) and 40mg/(kg·d). Normal control group, sham-operated group and model control group were given 5% DMSO.All of the groups were continuously intraperitoneal injected for 14 days. Compared the pain behavior in rats, the MIF and TNF-α levels in serum before and after treatment(7days, 14days). The expressions of MIF in sciatic nerve of rats were detected by western blot after treatment.Results: Part I : 7 days after treatment : the TNF-α levels in serum of block-treated group-1,2,3 and Res-treated group dropped significantly than model control group(P<0.05). 14 days after treatment : the pain threshold in rats of block-treated group-1,2,3 and Res-treated group increased than model control group(P<0.05), the MIF level in serum of Res-treated group was decreased(P<0.05)and block-treated group-1 was increased(P<0.05) than before, and block-treated group-2,3 had no significant difference from model control group(P>0.05), the expressions of p-p38 MAPK in sciatic nerve of block-treated group-1,3 and Restreated group were lower than model control group(P<0.05), the expression of p-p38 MAPK of block-treated group-2 was higher than normal control group(P<0.01).Part II : 7 days after treatment : the TNF-α levels in serum of targeted therapy group-1,2, Res-treated group-1,2 and model control group were declined than before(P<0.05), levels of targeted therapy group-2 and Res-treated group-1 were lower than targeted therapy group-1(P<0.05), and Res-treated group-2 has fallen to normal level, which was not different with normal control group(P>0.05). 14 days after treatment:the pain threshold in rats of targeted therapy group-2 and Res-treated group-1,2 were raised significantly than model control group(P<0.01), targeted therapy group-1 had no obvious distinction of model control group(P>0.05), the MIF levels in serum of targeted therapy group-2 and Res-treated group-1,2 were descended than model control group(P<0.05), the level of Res-treated group-2 was dropped apparently(P<0.01), which was distinct from targeted therapy group-2 and Res-treated group-1(P<0.05), the MIF level of targeted therapy group-1 was not other than before(P>0.05), the expression of MIF in sciatic nerve of targeted therapy group-1 kept on high level(was not differ from model control group, P>0.05), the expressions of targeted therapy group-2 and Res-treated group-1 were weaker than model control group(P<0.05), but higher than normal control group(P<0.05), the MIF expression of Res-treated group-2 kept at a low level, which closed to normal control group(P>0.05).Conclusion: MIF inhibitor(ISO-1), anti-CD74 antibodies, PD98059 and SB203580 have certain therapeutic effects to CRPS1 rats, so MIF is closely related to the pathological mechanism of CRPS1, the ERK1/2 and p38 MAPK pathways activated by MIF/CD74 may play important roles in CRPS1. The therapeutic efficacy of resveratrol on CRPS1 is positively correlated with injected dose, large dose of resveratrol[40mg/(kg·d)] have better curative effects than ISO-1(MIF inhibitor), the mechanism of action may be relative to the intervention of MIF/p38 MAPK signaling pathway. |
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