丙泊酚和地卓西平马来酸盐逆转抑郁大鼠电休克后的Tau蛋白过度磷酸化

Propofol compared with MK801 in reducing hyperphosphorylation of Tau protein induced by electroconvulsive shock in depressed rats

目的比较丙泊酚和地卓西平马来酸盐(MK-801)对抑郁大鼠电休克(ECT)后Tau蛋白过度磷酸化的影响及其机制。方法将嗅球切除抑郁模型大鼠分入6组,每组8只:对照组大鼠予5mL 0.9%氯化钠溶液腹腔内注射;MK-801组大鼠予5mL MK-801(10mg/kg)腹腔内注射;MK-801+ECT组大鼠予5mL MK-801(10mg/kg)腹腔内注射+施行1个疗程ECT;丙泊酚组大鼠予5mL丙泊酚(200mg/kg)腹腔内注射;丙泊酚+ECT组大鼠予5mL丙泊酚(200mg/kg)腹腔内注射+施行1个疗程ECT;ECT组大鼠予5mL0.9%氯化钠溶液腹腔内注射+施行1个疗程ECT。ECT后采用高效液相色谱法检测谷氨酸(Glu)在海马组织中的表达,免疫组织化学法和免疫印迹法检测p-AT8Ser202和糖原合成酶激酶(GSK)-3β1H8在海马组织中的表达。结果 ECT组、MK-801+ECT组和丙泊酚+ECT组的Glu含量分别显著高于对照组、MK-801组和丙泊酚组(P值均<0.01),丙泊酚组显著低于对照组(P<0.01),丙泊酚+ECT组显著低于ECT组(P<0.01),MK-801组与对照组间、MK-801+ECT组与ECT组间的差异均无统计学意义(P值均>0.05)。ECT组、MK-801+ECT组和丙泊酚+ECT组的p-AT8Ser202和GSK-3β1H8蛋白表达分别显著高于对照组、MK-801组和丙泊酚组(P值均<0.01),MK-801组和丙泊酚组均显著低于对照组(P值均<0.01),MK-801+ECT组、丙泊酚+ECT组均显著低于ECT组(P值均<0.05)。结论丙泊酚和MK-801可减缓ECT后Tau蛋白的过度磷酸化程度。

Objective To compare propofol with MK801 against the hyperphosphorylation of Tau protein induced by electroconvulsive shock in depressed rats. Methods Forty-eight adult depressed rats whose olfactory bulbs were removed were randomly divided into six groups （8 rats in each group）. Normal saline （5 mL） was injected peritoneally in control group. MK-801 （5 mL, 10 mg/kg） was injected peritoneally in MK-801 group. MK- 801 （5 mL, 10 mg/kg） was injected peritoneally and a course of electroconvulsive therapy （ECT） was performed in MK-801 ＋ ECT group. Propofol （5 mL, 200 mg/kg） was injected peritoneally in propofol group. Propofol （5 mL, 200 mg/kg） was injected peritoneally and a course of ECT was performed in propofol ＋ ECT group. Normal saline （5 mL） was injected peritoneally and a course of ECT was performed in ECT group. The concentration of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The expression of p-AT8^Ser202 and GSK-3β^1H8 in the hippocampus was measured by immunohistochemical method and Western blotting, respectively. Results The concentrations of glutamate in the ECT group, MK-801 ＋ ECT group and propofol ＋ ECT group were significantly higher than those in the control group, MK-801 group and propofol group （all P〈 0.01）. The concentration of glutamate in the propofol group was significantly lower than that of the control group （P〈0.01）. The concentration of glutamate in the propofol-I-ECT group was significantly lower than that in ECT group （P〈0.01）. There were no significant differences in the concentration of glutamate between MK-801 group and control group, or between MK-801 ＋ ECT group and ECT group （both P〉0.05）. The expression of p-AT8^Ser202 and GSK-3β^1H8 in the ECT group, MK-801 ＋ ECT group and propofol ＋ ECT group were significantly higher than those in the control group, MK-801 group and propofol group （all P〈0.01）. The expression of p-AT8^Ser202 and GSK-3β 1H8 in the MK-801 group and propofol group were significantly lower than those in the control group （all P〈 0.01）. The expression of p-AT8^Ser202 and GSK-3β^1H8 in the MK-801 ＋ ECT group and propofol ＋ ECT group were significantly lower than those in the ECT group （all P〈0.05）. Conclusion Both propofol and MK-801 can reduce the hyperphosphorylation of Tan protein induced by electroconvulsive shock.