Effect Of Sulforaphane On Expression Of IL-17and HO-1in Mice With Experimental Autoimmune Encephalomyelitis

Objective: To explore the effect of sulforaphane on expression of IL-17and HO-1in the brain and spinal cord of mice with experimental autoimmuneencephalomyelitis (EAE),we design and implement this experiment.Methods: The animal model was established in female C57BL/6micewith MOG35-55. Ninety-nine C57BL/6mice were randomly divided into fourgroups:18mice in control group,27mice in EAE group,27mice insulforaphane group,27mice in dexamethasone group. Furthermore, thegroups above were divided into three subgroups: premorbid group(13d),fastigium group(20d) and paracmastic group(30d). The mice in sulforaphanegroup were received sulforaphane(50mg/kg) by peritoneal injection everyother day, the mice in dexamethasone group were received dexamethasone(0.07mg/kg) by peritoneal injection every other day and the mice in controlgroup and EAE group received equal volume of physiological saline everyother day. The morbidity of disease, weight, and clinical signs were observeddaily. On day13ip,20ip and30ip, we execute the mice in four groupsrespectively. The pathological changes in brain and spinal cord were observedunder light microscopy after HE staining.The expression of IL-17and HO-1were observed by immunohistochemistry staining. The expression of HO-1protein in brain was determined by Western blot. Additionally, the levels ofIL-17mRNA and HO-1mRNA in the spinal cord of the groups above weremeasured by RT-PCR.Results:1No mice in control group have disease. Compared to EAE group, themobility, weight loss and mean clinical score of the mice in sulforaphanegroup and dexamethasone group were significantly lower(P<0.05).2In the premorbid, fastigium and paracmastic phases, pathological analysis(HE staining) demonstrated a significant decrease in the numbers ofinflammation cells in the brain and spinal cord of mice treated withsulforaphane and dexamethasone,compared to the EAE group mice(P<0.05)The inflammation cells in the brain and spinal cord of mice in EAE group,sulforaphane group and dexamethasone group increase significantly,compared with those in control group in three phases above(P<0.05).3In the premorbid, fastigium and paracmastic phases, the levels ofHO-1mRNA, HO-1protein and the number of HO-1positive cells in the brainand spinal cord of the mice in sulforaphane group increase obviously,compared with those in EAE group and dexamethasone group(P<0.05). Thelevels of HO-1mRNA, HO-1protein and the number of HO-1positive cells inthe brain and spinal cord of the mice in EAE group, sulforaphane group anddexamethasone group increase significantly, compared with those in controlgroup in three phases above(P<0.05).4In the premorbid, fastigium and paracmastic phases, the levels ofIL-17mRNA and the number of IL-17positive cells in the brain and spinalcord of the mice in sulforaphane group and dexamethasone group decreasesignificantly, compared with those in EAE group(P<0.05). The levels ofIL-17mRNA and the number of IL-17positive cells in the brain and spinalcord of the mice in EAE group, sulforaphane group and dexamethasone groupincrease significantly, compared with those in control group in three phasesabove(P<0.05).Conclusions:1There is an important relationship between the occurrence anddevelopment of EAE with IL-17and HO-1.2Sulforaphane inhibites the expression of IL-17and up-regulates theexpression of HO-1in the brain and spinal cord of mice with EAE, as well asameliorates the clinical severity of EAE. The neuroprotective effects of sulforaphane may be realized by activating Nrf2/ARE signal pathway.