Effect of tetramethylpyrazine on autophagy in hippocampal neurons of rats with sepsis-associated en-cephalopathy

Objective To evaluate the effect of tetramethylpyrazine on autophagy in the hippocampal neurons of rats with sepsis-associated encephalopathy. Methods Sixty SPF healthy male Sprague-Dawley rats, aged 11-14 weeks, weighing 200-240 g, were divided into 3 groups(n=20 each)using a random number table: sham operation group(group Sham), sepsis group(group Sep)and tetramethylpyrazine group(group TMP). Sepsis was induced by cecal ligation and puncture(CLP), and group Sham only underwent simple laparotomy.Tetramethylpyrazine 10 mg/kg was injected intraperitoneally at 1 h before CLP in group TMP.Morris water maze test was performed in 10 rats randomly selected at 12 and 36 h after CLP.Then the rats were sacrificed, and hippocampi were isolated for determination of the expression of microtubule-associated protein 1 light chain 3Ⅰ(LC3Ⅰ), LC3Ⅱ, Beclin-1 and p62 in hippocampal tissues by Western blot, and the LC3Ⅱ/LC3Ⅰratio was calculated. Results Compared with group Sham, the escape latency was significantly prolonged, the rate of time spent in the target quadrant was decreased, the LC3Ⅱ/LC3Ⅰratio was increased, the expression of Beclin-1 was up-regulated, and the expression of p62 was down-regulated at 12 and 36 h after CLP in group Sep and group TMP(P<0.05). Compared with group Sep, the escape latency was significantly shortened, the rate of time spent in the target quadrant was increased, the LC3Ⅱ/LC3Ⅰratio was decreased, the expression of Beclin-1 was down-regulated, and the expression of p62 was up-regulated at 12 and 36 h after CLP in group TMP(P<0.05). Conclusion The mechanism by which tetramethylpyrazine reduces sepsis-associated encephalopathy is related to inhibiting autophagy in the hippocampal neurons of rats. Key words: TETRAMETHYLPYRAZINE; Sepsis; Brain diseases; Autophagy; Hippocampus