Immunosuppression On Repair Of Nerve Regeneration After Sciatic Nerve Injury In Rats Of Experimental Research

Objective To observe the change of cyclophosphamide on Thl/Th2cytokine expressions, further to explore the effect of cyclophosphamide on peripheral nerve regeneration after injury and repair in rats. The findings of the research may provide theoretical basis for clinical therapy to peripheral nerve injury.Methods Ninety-six Wistar rats were randomly divided into cyclophosphamide treatment group (30rats), normal saline control group(30rats), sham group (30rats) and normal control group (6rats). The sciatic nerves of cyclophosphamide treatment group and normal saline control group were cut and sutured end-to-end, while the sciatic nerves of sham group were only expose and normal control group received no treatment. Cyclophosphane (15mg/kg.d)were intraperitoneally injected into rats of cyclophosphamide treatment group post-operatively for14days and normal saline were intraperitoneally injected into rats of other three groups for14days.Peripheral nerve regeneration and its related function were assessed by walking track analysis, recovery rate of sileus muscle weight and histomorphology. And immunohistochemistry stainings of INF-y, IL-4and IL-10was performed at1st,2nd,4th,8th, and12th after operation.Results Compared with normal saline control group,the recovery rate of sciatic nerve functional index (SFI) and recovery rate of sileus muscle weight were higher at8th,12th after operation(P<0.05). The diameter, number and thickness of myelin sheath of axons after nerve injury are better than the saline control group.There were no expressions of IFN-γ and IL-10in sciatic nerves of normal control group and sham group.However, there were no expressions of cyclophosphamide treatment group and normal saline control group. And there were no expressions of IL-4of all the groups at any time. The expression peaks of IFN-y were found at the1st week postoperatively in normal saline control group. Then, the expression decreased rapidly at the2nd week and disappeared at the4th week. In cyclophosphamide treatment group, the expression peaks of IFN-y was found at the2nd week, and extended to the4th week. There were no expressions of IFN-y at8th and12th. There were significant differences between the tow groups at1st,2nd,4th (P<0.05). The expression peaks of IL-10were found at the1st week postoperatively in normal saline control group. Then, the expression decreased gradually and there were little expressions of IL-10at8th week. The expressions of IL-10in cyclophosphamide treatment group at1st,2nd and4th were lower than normal saline control group, and there were significant differences of IL-10between the tow groups at8th. Conclusion1.Sciatic nerve transection may result in local immune reaction, Th1, Th2cells are activated and Th2immunity plays the key role.2. Cyclophosphamide is effective on accelerating the regeneration of peripheral nerve, which may be related to improve microenvironment for peripheral nerves regeneration and impact on Th1/Th2cytokine expressions.