| BackgroundIschemic stroke is one of the leading causes of death and disability in our country and even globally,but effective clinical treatments are still limited.Neuroinflammation is an important pathological mechanism of brain tissue damage and repair after ischemic stroke,and it is also a hotspot of current research.The nuclear factor erythroid2-related factor 2（Nrf2）/antioxidant response element（ARE）signaling pathway,as the main mechanism of endogenous and exogenous defense of cells and organisms,can regulate various biological processes such as inflammation and oxidative stressregulate inflammation,and so on.The downstream factor HO-1 has a strong anti-inflammatory effect,which is believed to be related to the polarization of macrophages and microglia.CDDO-Im is a synthetic triterpene derivative.At present,it has been found that it can effectively activate Nrf2/ARE pathway and play a significant anti-inflammatory effect in many disease models.ObjectiveTo explore the activation of Nrf2/ARE pathway in ischemic stroke rats after CDDO-Im intervention,and to explore the regulation of CDDO-Im on neuroinflammation and its effect on neurofunction in ischemic stroke rats.Methods1.Preparation of rat model:Sixty SD rats were selected and randomly divided into sham operation group（S group）,stroke group（M group）and CDDO-Im intervention group（M+C group）.The middle cerebral artery occlusion method was used in M group and M+C group to establish ischemic stroke model in rats,and rats with a score of 0 or 4were excluded.And the S group was given a sham operation（only the carotid artery was isolated,No suture was inserted）for control sham operation was used in S group to control.After operation,M+C group was injected with CDDO-Im（64μg/300g）through tail vein12h/time after operation,and S group and M group were given the same amount of normal saline at the same time as control.The rats in each group who died or did not meet the requirements for other reasons were randomly supplemented,and finally more than 18 rats in each group were guaranteed.2.Neurological evaluation:After 3 days,the nerve function of rats was measured by Longa score.3.Cerebral infarct size assessment:The cerebral infarct size of rats in each group was evaluated by 2,3,5-triphenyltetrazolium chloride staining.4.Protein level detection:The expression of Nrf2,heme oxygenated-1,ionic calcium binding adaptor molecule 1,interleukin-1β and interleukin-4 were detected by Western blot.Results1.CDDO-Im improves neurological scores in stroke rats:Compared with S group rats,M group rats showed significant neurological deficit and cerebral infarction area（P<0.001）.The neurological deficit score and cerebral infarction area of rats in M+C group were decreased compared with those in S group（P<0.05）.2.CDDO-Im can effectively activate the Nrf2 pathway and promote the expression of the downstream protein HO-1:There was no significant difference in the expression of Nrf2 protein in the nucleus of the M group compared with the S group,but the expression of HO-1 protein was increased（P<0.05）.The protein expressions of Nrf2 and HO-1 in the M+C group were increased（P<0.05）.3.CDDO-Im can modulate the neuroinflammation in post-stroke rats:Compared with group S,the expression of Iba1 protein in group M increased significantly（P<0.01）,the expression of IL-1 β and IL-4 protein also increased significantly（P<0.05）.Compared with the rats in the M group,the levels of Iba1 and IL-1β in the rats in the M+C group were decreased（P<0.05）,and the protein expression of IL-4 was further increased（P<0.05）.ConclusionCDDO-Im can activate the Nrf2/ARE pathway in ischemic stroke rats,and play a certain role in neuroprotection.The mechanism may be achieved by regulating neuroinflammation response and promoting the transformation of microglia to M2 type. |
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