Effect of ethyl pyruvate on cognitive function in sepsis rats

Abstract

Objective To determine the effect of ethyl pyruvate on cognitive function in rats with sepsis and its underling mechanism. Methods Part Ⅰ: The sepsis model was conducted by cecal ligation and puncture (CLP). Fifty healthy male SD rats were randomly divided into 5 groups (n=10): sham operation group (group C), sepsis group (group S), sepsis + High mobility group box-1 (HMGB1) treatment group (group SH), sham + HMGB1 treatment group (group H), sepsis + ethyl pyruvate treatment group (group SE). In the group SH and H, 5 μl of 0.5 μg/μl recombinant HMGB1 was injected into the lateral ventricle and 5 μl of saline was administered to the other 3 groups. In the SE group, ethyl pyruvate (80 mg/kg) was injected subcutaneously, and the remaining 4 groups were given the same volume of saline. Severn day survival curve analysis was performed among different groups. Part Ⅱ: Group dividing and experiment process are the same as before (n=20). Forty-eight hours after CLP or CLP sham a 6-days positioning navigation training of Morris water maze and the subsequent space exploration experiment was used to test cognitive ability. Part Ⅲ: Forty-eight hours post CLP or CLP sham, the brain tissue was harvest forbrain water content. Nissl′s staining was used to observe the number of neurons in the hippocampus and RT-qPCR was used to detect mRNA expression of hippocampal HMGB1, Ionized calcium bindingadaptor molecule-1 (Iba-1), Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and amyloid precursor protein (APP). Results (1) Compared to group C, the survival rate of group S and SH was significantly decreased (P 0.05). (2) There was no difference in swimming speed among the five groups in Morris water maze experiment. Compared to group C, swimming distance and escape latency were longer and the percentage of staying time passing through virtual platform and target quadrant decreased significantly (P 0.05). Compared with S group, the expression of HMGB1, TNF-α, IL-1β and Iba-1 other than APP mRNA was down-regulated in SE group. Conclusion Ethyl pyruvate can relieve cognitive dysfunction that induced by sepsis, which may be associated with inflammation reduction and blood-brain barrier function improvement. Key words: Ethyl pyruvate; Sepsis-associated encephalopathy; High-mobility protein group 1