Role of hippocampal HMGB1/RAGE signaling pathway in postoperative cognitive dysfunction in aged rats

Abstract

Objective To evaluate the role of hippocampal high-mobility group box 1 protein (HMGB1)/receptor for advanced glycation end products (RAGE) signaling pathway in postoperative cognitive dysfunction in aged rats. Methods Sixty-three healthy male Sprague-Dawley rats, aged 18 months, weighing 500-600 g, were randomly divided into 3 groups (n=21 each) using a random number table: control group (group C), splenectomy group (group S) and HMGB1 inhibitor ethyl pyruvate group (group EP). Ethyl pyruvate 40 mg/kg was injected intraperitoneally at 30 min after splenectomy in group EP, and the equal volume of solution without ethyl pyruvate was given in group S. Before operation and on days 1, 3 and 7 after operation, Morris water maze test was performed to assess the cognitive function, and the escape latency and ratio of time spent in the target quadrant were recorded.After completion of Morris water maze test on days 1, 3 and 7 after operation, 7 rats were sacrificed, and hippocampal tissues were obtained for determination of the expression of HMGB1 and RAGE (by Western blot) and HMGB1 and RAGE mRNA (by real-time polymerase chain reaction). Results Compared with group C, the escape latency was significantly prolonged, the ratio of time spent in the target quadrant was significantly decreased, and the expression of HMGB1 and RAGE protein and mRNA was significantly up-regulated on days 1 and 3 after operation in S and EP groups (P<0.05). Compared with group S, the escape latency was significantly shortened, the ratio of time spent in the target quadrant was significantly prolonged, and the expression of HMGB1 and RAGE protein and mRNA was significantly down-regulated on days 1 and 3 after operation in group EP (P<0.05). Conclusion Activation of hippocampal HMGB1/RAGE signaling pathway is involved in the development of postoperative cognitive dysfunction in aged rats. Key words: High mobility group proteins; Advanced glycation end product-specific receptor; Hippocampus; Cognition disorders; Postoperative complications; Aged