不同剂量异丙酚联合电休克对抑郁大鼠海马突触素表达的影响

Effect of different doses of propofol on synaptophysin level in hippocampus of mentally depressed rats after electroconvulsive therapy

目的探讨不同剂量异丙酚联合电休克对抑郁大鼠海马突触素（SYP）表达的影响。方法成年雄性SD大鼠50只，体重200—250g，随机分为5组（n=10）：对照组（c组）、抑郁组（D组）和低、中、高剂量异丙酚联合电休克组（M。组）。C组正常饲养，余4组制备慢性不可预见性轻度应激抑郁模型，模型制备成功后，c组和D组腹腔注射生理盐水10ml／kg，M1-3组分别腹腔注射异丙酚90、110、130mg／kg后行电休克治疗，每天处理1次，连续7d。于造模前1d、建模后1d、处理结束后1d采用openfield测试和糖水消耗实验观察行为学。采用免疫组织化学法检测海马CA3区SYP蛋白表达，RT-PCR法检测海马SYPmRNA表达。结果与c组比较，余4组建模后1d水平计分、垂直计分及理毛次数减少，中央格停留时间延长，糖水消耗比下降（P〈0．05）；与D组比较，M1组和M2组处理结束后1d水平计分、垂直计分理毛次数增加，中央格停留时间缩短，糖水消耗比升高，SYP蛋白及其mRNA表达上调（P〈0．05）；与M1组和M2组比较，M3组处理结束后1d水平计分、垂直计分及理毛次数减少，中央格停留时间延长，SYP蛋白及其mRNA表达下调（P〈0．05）。结论异丙酚90mg／kg和110mg／kg联合电休克治疗可在一定程度上改善大鼠的抑郁状态；而异丙酚130mg／kg联合电休克对抑郁状态无明显改善，其机制可能与大剂量异丙酚过度抑制大鼠电休克后海马SYP的表达有关。

Objective To investigate the effects of different doses of propofol on expression of synaptophysin （SYP） mRNA and protein in the hippocampus of mentally depressed rats after electroconvulsive therapy （ECT）. Methods Fifty adult male SD rats weighing 200-250 g were randomly divided into 5 groups （ n = 10 each） ： group I control （group C） ; group II mental depression （group D） ; group III, IV, V propofol 90, 110, 130 mg/kg ＋ ECT （group M1, M2, M3 ）. Mental depression was induced by isolation and chronic unpredictable mild stress （CUMS） in group II-V . Group M1, M2 and M3 received intraperitoneal （IP） propofol 90, 110 and 130 mg/kg respectively ＋ ECT once a day × 7 consecutive days while group C and D received IP normal saline instead of propofol. The rats underwent open field test and sucrose liquid consumption test the day before and after mental depression was established and one day after treatment. The rats were killed after the last test for determination of expression of SYP mRNA （by RT-PCR） and protein （by immuno-histochemistry） in the hippocampns. Results The ambulation scores, rearing scores, grooming time and sucrose consumption percentage were significantly decreased while the center,grid detention time （CDT） was significantly increased in group II- V as compared with control group indicating mental depression was successfully induced. The ambulation scores, rearing scores, grooming time, sucrose consumption percentage, SYP mRNA and protein expression were significantly increased while CDT was significantly decreased after treatment in group M1 and M2 as compared with group D indicating that propofol 90 or 110 mg/kg combined with ECT was effective for the treatment of mental depression. Conclusion Propofol 90 or 110 mg/kg combined with ECT is effective in treating mental depression while proprofol 130 mg/kg combined with ECT is not. Excessive inhibition of SYP expression in hippocampus by large dose of propofol may explain the mechanism.