The Impact Of Hippocampal HMGB1 And RAGE On Postoperative Cognitive Dysfunction Of Aged Rats After Splenectomy

Objective:Postoperative cognitive dysfunction（POCD）is one of the common complications after surgery and anesthesia in elderly patients.The pathogenesis is associated with cytokine-mediated inflammatory response.High mobility group protein 1（HMGB1）is a highly conserved non-histone nucleoprotein.HMGB1 is considered to be"late inflammatory factor"when it released to extracellular.The receptor for advanced glycation end products（RAGE）is a receptor for the HMGB1signaling pathway and has a high affinity for HMGB1.Inflammatory reactions in animals with POCD are present in central system and the periphery.In this study,the impact of HMGB1/RAGE signal pathway on POCD and the possible mechanism of POCD were investigated by studying the expression of HMGB1 and RAGE in hippocampus after splenectomy in aged rats.Methods:Sixty-three healthy male aged Sprague-Dawley rats,16-18 months old,weighing about 500-600 g were selected and divided into 3 groups（n=21）according to the method of random number table:control group（group C）,surgery group（group S）and ethyl pyruvate group（group EP）.No intervention was made in Group C;After splenectomy at 30 min,group EP received intraperitoneal injection of ethyl pyruvate solution(40 mg×kg^-1),and group S received intraperitoneal injection of equal volume solution without ethyl pyruvate.Rats were trained with positioning sailing and space exploration for 5 days preoperatively.The cognitive function was evaluated preoperatively and at 1 d,3 d and 7 d postoperatively by Morris water maze.The escape latency and the ratio of time spent in the target quadrant would be recorded by smart junior system.7 rats were killed respectively at 1 d,3 d,7 d after surgery and Morris water maze test.Hippocampal tissue was extracted.The expression of HMGB1 and RAGE protein in hippocampus will be measured by Western Blot methods,and the expression of HMGB1 and RAGE mRNA in hippocampus will be measured by RT-PCR methods.Results:（1）Compared with preoperative results,the escape latency was significantly extended and the ratio of time spent in the target quadrant was declined in group S at 1 d,3 d after surgery（P（27）0.05）.（2）Compared with results of group C,the escape latency was extended and the ratio of time spending in the target quadrant was declined in group S at 1 d,3 d after surgery（P（27）0.05）,as well as the expression of HMGB1 and RAGE in hippocampus were obviously increased up-regulated（P<0.05）;Compared with results of group S,the escape latency was obviously declined and the ratio of time spent in the target quadrant was extended and the expression of HMGB1 and RAGE were decreased in group EP at 1 d,3 d after surgery（P<0.05）.Conclusion:（1）The expression of HMGB1 and RAGE up-regulated in aged rats after splenectomy.（2）The increased HMGB1 and RAGE level in hippocampus may be involved with cognitive dysfunction after the splenectomy in aged rats.