| Objective： Part I: Recent studies have found that Nrf2(nuclear transcription factor-2)/ARE (antioxidant response element) signaling pathway play important role inoxidative stress response,anti-inflammatory and neuroprotective role in vivo. Thispart of the study we use sulforaphane activates the Nrf2-ARE signaling pathway,retinoic acid inhibits the Nrf2-ARE signaling pathway to observed and explore themechanisms of neuroprotection of Nrf2-ARE signaling pathway of intracerebralhemorrhage; Part II: literature brain injury in various parts of the brain activation andproliferation of endogenous neural stem cells, and on the perihemorrhage damagedarea migration, but the mechanism is not clear. The part observed and explore themechanisms of the TGF-beta on how activated endogenous neural stem cellproliferation of intracerebral hemorrhage.Methods: Part I: We use SD rat basal ganglia injection of autologous arterialintracerebral hemorrhage model, divided into four groups: the purely intracerebralhemorrhage group, sulforaphane (Nrf2activation agent, SFN) treatment ofintracerebral hemorrhage and retinoic acid (RAthe Nrf2inhibitor) treatment ofintracerebral hemorrhage and normal control group, observed at different time pointsneurological function in rats, the brain tissue was detected by immunohistochemistry,immunofluorescence and Western blot analysis Nrf2, HO-1, NF-κB expression. Thedata were statistically analyzed to observe the role of brain hemorrhage andneuroprotection. Part II: SD rat basal ganglia autologous arterial injection method toestablish a model of intracerebral hemorrhage were randomly divided into shamoperation group, intracerebral hemorrhage in the experimental group alone, accordingto1D,7d,14d,21d divided into four subgroups, the effects of different neurologicalfunction score, point-in-time line double immunofluorescent labeling check theco-expression of Nestin and BrdU immunohistochemistry TGF-beta expression inbrain tissue. The data were statistically analyzed to observe the role of brainhemorrhage and neuroprotection.Results: Part I: SFN treatment activate Nrf2rat group after intracerebral hemorrhage and compared to the purely intracerebral hemorrhage group, the neurologicaldysfunction significantly reduced; purely intracerebral hemorrhage group andcompare SFN treatment activated Nrf2rats group immunofluorescence, Western blotdetection of Nrf2transcription factor, HO-1anti-oxidation protein expression wereincreased in RA treatment of intracerebral hemorrhage72h and reached the peakvalue, SFN treatment activated Nrf2rats group decreased NF-kappaB expression,immunohistochemical detection of intracerebral hemorrhage microglial activation;ratshighest mortality, serious neurological damage detection Nrf2transcription factor, theexpression of HO-1anti-oxidation protein compared with SFN intervention groupand the group of intracerebral hemorrhage, persistent inhibition may last about fivedays of RA treatment inhibits Nrf2.The rat group decreased NF-kappaB expression,detected by immunohistochemistry suggesting that intracerebral hemorrhagemicroglial activation obvious and duration to5days. Part II: In this study, we canobserved follows:1) purely intracerebral hemorrhage immune double-labeled positivecells expressed7d, persistent increased to21d,2) sham-operated group comparedwith intracerebral hemorrhage group7d,14d,21d double-labeled positive cells of theimmune, the differences were statistically significant (P <0.01). After intracerebralhemorrhage does the activation of endogenous neural stem cell proliferation.3) shamoperation group TGF-beta expression in the cytoplasm there is less. Purelyintracerebral hemorrhage group no significant increase in TGF-beta-positive cells at1d,3d began to increase, we can see a large number of pulp colored positive cells,7dreached a peak, persistent increased to21d. TGF-beta expression after intracerebralhemorrhage associated with endogenous neural stem cells may be involved inendogenous neural stem cell activation proliferation.Conclusion:1) Acute inflammatory injury on intracerebral hemorrhage model;2)Sulforaphane activated Nrf2-ARE signaling pathway can be increased HO-1, NQO1antioxidant enzyme expression, reduce perihemorrhage inflammatory reaction afterintracerebral hemorrhage, improve the neuroprotective effect;3) microglial earlyactivation play neurotoxicity after intracerebral hemorrhage;4) ENSCs activation,proliferation, was increased gradually in7-21days after intracerebral hemorrhage;5)TGF-beta signaling pathway may be play important role in ENSCs activation proliferation intracerebral hemorrhage. |
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