摘要
目的探讨柴胡疏肝散对慢性不可预见性温和应激(CUMS)抑郁模型大鼠的抗抑郁作用机制。方法将48只SD大鼠随机分为正常组8只和建模组40只,建模组采用CUMS结合孤养方法构建大鼠抑郁模型,建模周期28 d。建模成功后将40只建模组大鼠随机平均分为模型组、文拉法辛组、低剂量组、中剂量组、高剂量组。低、中、高剂量组分别给予1.125、2.250、4.500 g/mL柴胡疏肝散药液,文拉法辛组给予3 mg/mL文拉法辛溶液,正常组及模型组给予生理盐水,每日各组均按体质量0.5 mL/100 g灌胃1次,连续14 d,除正常组外,其余各组继续给予CUMS。测量并观察各组体质量变化,采用糖水偏好指数、强迫游泳不动时间比较各组大鼠的行为学变化,采用蛋白印迹法(Western blot)检测海马组织p-PI3K、PI3K、p-Akt、Akt蛋白相对表达量并计算p-PI3K/PI3K、p-Akt/Akt比值,采用酶联免疫吸附试验(ELISA)检测海马组织去甲肾上腺素(NE)和5-羟色胺(5-HT)含量变化。结果与正常组比较,模型组体质量、糖水偏好指数显著降低(P均<0.01),强迫游泳不动时间显著升高(P<0.01),海马组织p-PI3K/PI3K、p-Akt/Akt显著降低(P均<0.01),NE、5-HT含量均明显降低(P均<0.01);与模型组比较,文拉法辛组、低剂量组、中剂量组、高剂量组体质量、糖水偏好指数均升高(P均<0.05或0.01),强迫游泳不动时间均降低(P均<0.05或0.01),文拉法辛组、中剂量组、高剂量组p-PI3K/PI3K、p-Akt/Akt升高(P均<0.05或0.01),NE、5-HT含量均显著升高(P均<0.01);与文拉法辛组比较,低剂量组糖水偏好指数降低,p-PI3K/PI3K、p-Akt/Akt降低(P均<0.05),其余差异无统计学意义(P均>0.05)。结论柴胡疏肝散能改善CUMS抑郁模型大鼠抑郁行为,其机制可能与激活PI3K/Akt信号通路、增加海马NE和5-HT含量相关。
Objective:To study the antidepressant effect of Chaihu Shugan powder in depression model rats with chronic unpredictable mild stress(CUMS).Methods:A total of 48 SD rats were randomly divided into normal group(n=8)and modeling group(n=40).In the modeling group,CUMS combined with solitary rearing method was used to construct the rat depression model,and the modeling period was 28 days.40 successful modeled rats were randomly divided into model group,venlafaxine group,low-dose group,medium-dose group and high-dose group.The rats in low-dose,medium-dose and high-dose groups were given Chaihu Shugan powder 1.125,2.250 and 4.500 g/mL respectively,the rats in venlafaxine group were given venlafaxine 3 mg/mL,and the rats in the normal and model groups were given normal saline.According to body weight,all groups were given relevant medicine intragastric administration of 0.5 mL/100 g,once a day,for consecutive 14 days,and CUMS was continued in all groups except the normal group.Body weight changes of mice were measured;the behavioral changes of each group were compared by sucrose preference index and forced swimming immobility time;the protein expression levels of p-PI3K,PI3K,p-Akt and Akt in hippocampus were detected by Western blot;the contents of norepinephrine(NE)and 5-hydroxytryptamine(5-HT)in hippocampus were detected by ELISA.Results:Compared with the normal group,the body weight and sucrose preference index in the model group significantly decreased(P<0.01),the forced swimming immobility time significantly increased(P<0.01),the ratios of p-PI3K/PI3K and p-Akt/Akt in hippocampus significantly decreased(P<0.01),and the contents of NE and 5-HT significantly decreased(P<0.01).Compared with the model group,the body weight and sucrose preference index in venlafaxine,low-dose,medium-dose and high-dose groups were significantly increased(P<0.05 or 0.01),and the forced swimming immobility time significantly decreased(P<0.05 or 0.01);the ratios of p-PI3K/PI3K and p-Akt/Akt in the venlafaxine,medium-dose and high-dose groups significantly increased(P<0.05 or 0.01),and the contents of NE and 5-HT significantly increased(P<0.01).Compared with the venlafaxine group,the sucrose preference index and the ratios of p-PI3K/PI3K and p-Akt/Akt significantly decreased in the low-dose group(P<0.05),and there was no significant difference in other indicators.Conclusion:Chaihu Shugan powder can improve the depressive symptoms of CUMS depression model rats,and its mechanism may be related to the activation of PI3K/Akt signaling pathway and the increase of contents of NE and 5-HT.
作者
滕海英
肖建平
付仰志
石小峰
TENG Haiying;XIAO Jianping;FU Yangzhi;SHI Xiaofeng(Rehabilitation Hospital,Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350003,China;Fujian Key Laboratory of Rehabilitation Technology,Fuzhou,Fujian 350003,China)
出处
《福建中医药》
2022年第12期19-22,共4页
Fujian Journal of Traditional Chinese Medicine
基金
中央引导地方科技发展专项(2018L3009)
福建省卫生健康科技计划项目(2020QNA070)。
