The Role Of HMGB1 In Sepsis Rats With Cognitive Dysfunction

OBJECTIVE To investigate the role of HMGB1 in cognitive dysfunction by cecal ligation and puncture sepsis rats model.METHODS First part: Fifty male SD rats were randomly divided into five groups(n=10): sham control(group S),sepsis(group C),sepsis+recombinant HMGB1 group(group CH),sham+ recombinant HMGB1 group(group H),sepsis + pyruvate treated group(group CE);sepsis rat model was made by cecal ligation and puncture,post operation rats in group CH and H were treated with recombinant HMGB1(0.5ug/ul,5ul)by intracerebroventriclar injection,the remaining three group administration of saline;group CE subcutaneous injection with 80mg/kg pyruvate,the other four group administration of same capacity saline;then the seven day mortality was observed;The second part of the experiment: SD rats were randomly divided into five groups(n=20)and treated according to the first part,Spatial learning and memory were evaluated by Morris Water Maze(MWM)after 48h;The last part of the experiment(30rats/group):brain water content was detected in five rats each group and the number of neurons in hippocampus morphology was measured by nissl staining,immunohistochemical detection of the expression of HMGB1,the m RNA levels of HMGB1、Iba-1、TNF-α、IL-1β and APP were measured by Real-time q PCR.RESULTS(1)The survival time of rats in group C group CH and group CE were significantly decrease compared with that in group S(P <0.05).(2)The place navigation test of Morris water maze find there are dierences in swimming distance and escape latency(P<0.05);compared with group S,we find the frequencies cross the assum platform and percentage of target quadrant in spatial probe test were decrease in the other four group(P<0.05).(3)Compared with group S,rats brain water content were increase in the remaining four groups and lower in group CE,the water content of group H was higher than group S but lower than group C(P<0.05).(3)Nissl staining show that compared with group S the number of neurons in hippocampus were decrease in the remaining four groups,compared with group C the number of neurons in hippocampus were decrease in group CH and that higher in group CE(P<0.05).(4)Levels of HMGB1、TNF-α、IL-1β、Iba-1 and the APP were upregulated in the hippocampus of sepsis rats and this effect can be enhanced by recombinant HMGB1(P<0.05).CONCLUSION Sepsis can lead to impair of learning and cognitive function,blood-brain barrier damage and excessive expression of inflammatory factors associated with this,upregulation of HMGB1 cause the excessive activation of microglia,inhibit HMGB1 can improve the cognitive dysfunction caused by sepsis.