小檗碱对抑郁小鼠脑海马组织能量代谢的影响

Effects of berberine on energy metabolism of hippocampus in depression mice

目的:研究小檗碱对抑郁小鼠海马内能量代谢水平的影响。方法:雄性ICR小鼠随机分为正常组和刺激组。刺激组采用慢性不可预知性温和刺激建立抑郁模型。4周后进行糖水偏爱实验(SPT),并依据糖水偏爱比一致的原则将刺激组重新分为模型组,小檗碱低、中、高剂量组(50、100、200mg/kg)和氟西汀组(20mg/kg),每组8只。各组以10mL/kg灌胃给药,正常组和模型组以等体积0.9%氯化钠溶液灌胃。连续给药4周后采用强迫游泳实验(FST)和SPT来评价小鼠抑郁样行为,生化试剂盒检测海马三磷酸腺苷(ATP)、ATP酶、丙酮酸和乳酸含量,Western Blot检测腺苷酸活化蛋白激酶(AMPK)的蛋白表达量。结果:与正常组比较,模型组小鼠FST不动时间显著延长(P<0.01),SPT糖水偏爱比显著降低(P<0.01),海马内ATP含量显著降低(P<0.05)。与模型组比较,小檗碱各剂量组FST不动时间均显著缩短(P<0.05,P<0.01),糖水偏爱比显著升高(P<0.05,P<0.01),小檗碱中、高剂量组乳酸和丙酮酸含量显著减少(P<0.05,P<0.01),AMPK的蛋白表达显著升高(P<0.05,P<0.01),小檗碱中剂量组ATP含量显著增加(P<0.01)。结论:小檗碱的抗抑郁作用可能与激活AMPK,促进ATP产生,提高海马内能量水平有关。

Objective:To investigate the effects of berberine on energy metabolism in the hippocampus of depressed mice.Methods:Male ICR mice were randomly divided into normal group and stimulation group.The stimulation group subjected to chronic unpredictable mild stress.The sucrose preference test(SPT)was performed after 4 weeks,and then the stimulation group was reclassified into the model group,the low,medium and high doses of berberine(50,100,200mg/kg)groups and the fluoxetine(20mg/kg)group according to the principle of consistent reference of sugar and water,8 mice per group.Each group was given the corresponding drugs for 10mL/kg,the normal group and model group were given 0.9%sodium choloride solution.After 4 weeks of continuous administration,forced swimming test(FST)and SPT were used to evaluate the depression like behavior of mice.The contents of adenosine triphosphate(ATP),ATPase,pyruvate and lactate in hippocampus were measured by biochemical kit.Western Blot was used to detect the protein expression of Adenosine 5’-monophosphate-activated protein kinase(AMPK).Results:Compared with the control group,the immobility time of FST in the model group significantly prolonged(P<0.01),the sucrose preference of SPT significantly decreased(P<0.01),and the content of ATP in the hippocampus significantly decreased(P<0.05).Compared with the model group,the immobility time of FST in every dose berberine groups significantly decreased(P<0.05,P<0.01),the SPT significantly increased(P<0.05,P<0.01),the content of lactic acid and pyruvate in high and middle dose berberine groups significantly decreased(P<0.05,P<0.01),and the protein expression of AMPK significantly increased(P<0.05,P<0.01).The ATP content of middle dose berberine group significantly increased(P<0.01).Conclusion:The antidepressant effect of berberine may be related to the activation of AMPK,the promotion of ATP production and the improvement of energy level in hippocampus.