The Effect Ion And Mechanism Of Dexmedetomidine Postconditioning On Ischemia-reperfusion Injury To Rats’ Brain

Cerebral ischemia-reperfusion induced injury is one of the most common complications during perioperation period, which will result in injury of brain’s function and is usually associated with increased duration of hospital stay and healthcare cost.Despite lots of interventions have been invented to restore blood supply of ischemia area,there have been no effective treatments in the clinical practice for secondary cerebral ischemia-reperfusion at present.Recently, some studies have proved that apoptosis and inflammatory reaction mediated via TLR4 are the critical mechanisms leading to cerebral I/R.Trigger of anti-apoptosis signal cascade to reduce cerebral cell’s apoptosis or inhibition of TLR4 signaling to relieve inflammation are becoming a novel a strategy to ameliorate cerebral I/R.Dexmedetomidine is effective in anti-inflammatory and potential neuroprotective function perioperative period,but the mechanism is uncertain.We suppose that DEX protect the cerebrum by inhibiting inflammation induced by cerebral ischemia-reperfusion. This study includes two parts:1. The neuroprotection induced by dexmedetomidine postconditioning in rats under brain middle cerebral artery obstructionObjective:To investigate the effects of DEX postconditioning against cerebral ischemia-reperfusion injury in rats. Methods:24 adult male Sprague-Dawley rats were randomly assigned into control group, Ischemia reperfusion group (I/R), Ischemia reperfusion+DEX group(D). Right middle cerebral artery occlusion (MCAO) model was made by Zea Longa method. The spatial learning and memory functions were measured with Morris water maze task at 4d of reperfusion. Ultrastructure changes of hippocampal CA1 neurons and the parietal cortex were examined under electron microscopy at 7d of reperfusion.Results:1.1 Results of the water maze test:the shorter escaping latency period is,the sooner the speed of learn and memory functions are.It was found in the Morris water maze test that escaping latency period of rats in group D and group I/R was significantly longer, and between the two groups, the escaping latency period in group D was shorter. Significant difference exists.The times cross platform and stay in the second quadrant were used to judge the memory ability. In this study, we found that the times cross platform and stay in the second quadrant of rats in group D and group I/R were shorter,and between the two groups, the times of cross plat and stay in the second quadrant of rats in group I/R were much shorter.1.2 The changes of cerebral ultrasructure:the Nissle staining conclusion indicates complete and marshalling cell structure,clear endohylema and nucleus,big,round and clear nucleolus,and blue netron in the frontal cortex and hippocampal neuron in the control group.However,the neurons demonstrate shallow pigmentation,decreased number,confused assay,increased cellular gap,irregular cell shapes,decreased nucleus,chromatin margination and concentration in the I/R group.The difference is significant in the two groups(P< 0.01).Most of the neurons in the group D survive in comparison with the I/R group and the difference is significant(P< 0.01).2. The effects of dexmedetomidine on the expression of TLR4 proteins and HMGB1 level in rats brain tissue after cerebral ischemia-reperfusion injuryObjective:To investigate the effects of DEX on TLR4 and HMGB1 in rats brain tissue after ischemia-reperfusion. Methods:24 adult male Sprague-Dawley rats were randomly assigned into control group(C), Ischemia reperfusion group (I/R), Ischemia reperfusion+DEX group (D) and atip+post-DEX group. Right middle cerebral artery occlusion (MCAO) model was made by Zea Longa method.Immuohistochemistry and Western blot for expression of cerebral TLR4, ELISA for HMGB1 level.Results:The expression of TLR4 proteins and HMGB1 level in group I/R were significantly increased after cerebral ischemia 2h and reperfused 24h compared with group C and group D.The expression of TLR4 proteins and HMGB1 level in group D were significantly decreased compared with group I/R.Atip 250ug/kg partially suppressed the downregulated effects of DEX on TLR4 and HMGB1.Conclusions1.Postcondtion with DEX provides cerebral protection against ischemia-reperfusion injury in rats model of MCAO,and it can improve the cognitive function of those rats.2.DEX provides cerebral protection by reducing the expression of TLR4 proteins and HMGB1 level though activates α2AR.