菖郁逍遥方治疗慢性乙型肝炎伴抑郁症的临床疗效及作用机制探讨
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摘要
目的观察菖郁逍遥方治疗慢性乙型肝炎(chronic hepatitis B,CHB)伴抑郁症的临床疗效,并探讨其作用机制。方法 90例慢性CHB伴抑郁症患者,采用随机数字表法分为治疗组45例,对照组45例。在恩替卡韦治疗的基础上,对照组服用氟哌噻吨美利曲辛片;治疗组服用中药复方菖郁逍遥方,疗程12周。以汉密尔顿抑郁量表17项(Hamilton depression scale,HAMD_(17))评分观察治疗前、治疗中(治疗4周)、治疗后(治疗12周)两组患者的抑郁状态变化;以副反应量表(treatment emergent symptom scale,TESS)观察两组治疗后副反应;观察治疗前后血清ALT活性、乙型肝炎病毒DNA(hepatitis B virus DNA,HBV DNA)定量、5-羟色胺(5-hydroxytryptamine, 5-HT)、去甲肾腺上素(norepinephrine, NE)、脑源性神经营养因子(brain derived neurotrophic factor,BDNF)水平及内源性大麻素:N-花生四烯酸氨基乙醇(Arachidonoylethanolamine,AEA)、2-花生四烯酸甘油(2-arachidonoylglycerol,2-AG)及其受体(cannabinoid receptor,CBR)1、2指标变化。结果两组治疗中、治疗后的HAMD_(17)评分较治疗前均明显降低(P<0.05,P<0.01),治疗后治疗组的总有效率与对照组相似但安全性评价较高。治疗后,治疗组HBV DNA阴转率、ALT复常率均较对照组高(P<0.05)。两组血清5-HT、NE、BDNF均较治疗前显著升高(P<0.05,P<0.01)。两组治疗后血清AEA、2-AG、CBR1水平较前增加(P<0.05),且以治疗组效果显著;CBR2含量较治疗前无明显变化(P>0.05)。结论菖郁逍遥方具有显著改善CHB患者抑郁状态的临床疗效,作用机制与通过调控内源性大麻素水平来升高单胺类神经递质、BDNF相关。
Objective To study the efficacy of Changyu Xiaoyao Recipe(CYXYR) in treating chronic hepatitis B(CHB) patients with depression and to further explore its mechanism. Methods Totally 90 CHB patients with depression were randomly assigned to the treatment group and the control group, 45 cases in each group. On the basis of Entecavir treatment, patients in the treatment group additionally took CYXYR, while those in the control group took Flupentixol and Melitracen Tablet. The treatment course for all was 12 weeks. Hamilton Depression Scale(HAMD) score, ALT activities, quantitation of hepatitis B virus DNA(HBV DNA), levels of 5-hydroxytryptamine(5-HT), norepinephrine(NE), brain derived neurotrophic factor(BDNF),endogenous cannabinoids AEA,2-AG,CBR1,CBR2 were determined before treatment,during treatment(at 4 weeks of treatment)and after treatment(at 12 weeks of treatment).Results The scores of HAMD were significantly lower in the two groups during and after treatment,as compared with before treatment(P<0.05,P<0.01).The total effective rate of the treatment group was similar to that of the control group,but the safety evaluation was higher.Post-treatment HBV DNA negative conversion rate and ALT recovery rate were higher in the treatment group than in the control group(P<0.05).Serum levels of 5-HT,NE,and BDNF were significantly higher after treatment than before treatment in both groups(P<0.05,P<0.01).After treatment serum levels of AEA,2-AG,and CBR1 increased more than before treatment in the two groups(P<0.05),and better effects were obtained in the treatment group.CBR2 content had no significant change after treatment in the two groups,as compared with before treatment(P>0.05).Conclusions CYXYR could significantly improve the state of depression in CHB patients with less adverse reactions.The mechanism was closely related to elevating monoamine neurotransmitters and BDNF by regulating endogenous cannabinoid levels.
Objective To study the efficacy of Changyu Xiaoyao Recipe(CYXYR) in treating chronic hepatitis B(CHB) patients with depression and to further explore its mechanism. Methods Totally 90 CHB patients with depression were randomly assigned to the treatment group and the control group, 45 cases in each group. On the basis of Entecavir treatment, patients in the treatment group additionally took CYXYR, while those in the control group took Flupentixol and Melitracen Tablet. The treatment course for all was 12 weeks. Hamilton Depression Scale(HAMD) score, ALT activities, quantitation of hepatitis B virus DNA(HBV DNA), levels of 5-hydroxytryptamine(5-HT), norepinephrine(NE), brain derived neurotrophic factor(BDNF),endogenous cannabinoids AEA,2-AG,CBR1,CBR2 were determined before treatment,during treatment(at 4 weeks of treatment)and after treatment(at 12 weeks of treatment).Results The scores of HAMD were significantly lower in the two groups during and after treatment,as compared with before treatment(P<0.05,P<0.01).The total effective rate of the treatment group was similar to that of the control group,but the safety evaluation was higher.Post-treatment HBV DNA negative conversion rate and ALT recovery rate were higher in the treatment group than in the control group(P<0.05).Serum levels of 5-HT,NE,and BDNF were significantly higher after treatment than before treatment in both groups(P<0.05,P<0.01).After treatment serum levels of AEA,2-AG,and CBR1 increased more than before treatment in the two groups(P<0.05),and better effects were obtained in the treatment group.CBR2 content had no significant change after treatment in the two groups,as compared with before treatment(P>0.05).Conclusions CYXYR could significantly improve the state of depression in CHB patients with less adverse reactions.The mechanism was closely related to elevating monoamine neurotransmitters and BDNF by regulating endogenous cannabinoid levels.
引文
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[11] 陈少东, 王宏国, 杨嘉恩, 等. 菖郁逍遥方联合恩替卡韦分散片治疗慢性乙型病毒性肝炎伴抑郁症35例临床观察[J]. 中医杂志, 2015, 56(14), 1208-1211.
[12] Luchicchi A, Pistis M. Anandamide and 2-arachidonoylglycerol: pharmacological properties, functional features, and emerging specificities of the two major endocannabinoids[J]. Mol Neurobiol, 2012, 46(2): 374-392.
[13] Evanson NK, Tasker JG, Hill MN, et al. Fast feedback inhibition of the HPA axis by glucocorticoids is mediated by endocannabinoid signaling[J]. Endocrinology, 2010, 151(10): 4811-4819.
[14] Díaz-Alonso J, Guzmán M, Galve-Roperh I. Endocannabinoids via CB1 receptors act as neurogenic niche cues during cortical development. [J]. Philos Trans R Soc Lond B Biol Sci, 2012, 367(1607): 3229-3241.
[2] Riebe CJ, Wotjak CT. Endocannabinoids and stress[J]. Stress, 2011, 14(4): 384-397.
[3] Mechoulam R, Parker LA. The endocannabinoid system and the brain[J]. Annu Rev Psychol, 2013, 64: 21-47.
[4] 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015年版)[J]. 中国肝脏病杂志(电子版), 2015, 7(3): 1-18.
[5] 中华医学会. 临床诊疗指南: 精神病学分册[M]. 北京: 人民卫生出版社, 2007: 44-47.
[6] 中国中医药学会内科肝病专业委员会. 病毒性肝炎中医辨证标准(试行)[J]. 中医杂志, 1992, 33(5): 39.
[7] 张明圆. 精神科评定量表手册[M]. 长沙: 湖南科学技术出版社, 1998: 96-98.
[8] 郭兰婷, 万云, 单友荷. 中国精神障碍分类与诊断标准孤独症诊断标准的临床研究[J]. 中华精神科杂志, 2002, 35(3), 162.
[9] 中华医学会, 中国精神障碍防治指南丛书[M]. 北京: 北京大学医学出版社, 2015: 78-81.
[10] 张建生. 疏肝解郁法治疗慢性乙型病毒性肝炎伴焦虑抑郁障碍的临床研究[J]. 中华中医药学刊, 2012, 30(6): 1422-1423.
[11] 陈少东, 王宏国, 杨嘉恩, 等. 菖郁逍遥方联合恩替卡韦分散片治疗慢性乙型病毒性肝炎伴抑郁症35例临床观察[J]. 中医杂志, 2015, 56(14), 1208-1211.
[12] Luchicchi A, Pistis M. Anandamide and 2-arachidonoylglycerol: pharmacological properties, functional features, and emerging specificities of the two major endocannabinoids[J]. Mol Neurobiol, 2012, 46(2): 374-392.
[13] Evanson NK, Tasker JG, Hill MN, et al. Fast feedback inhibition of the HPA axis by glucocorticoids is mediated by endocannabinoid signaling[J]. Endocrinology, 2010, 151(10): 4811-4819.
[14] Díaz-Alonso J, Guzmán M, Galve-Roperh I. Endocannabinoids via CB1 receptors act as neurogenic niche cues during cortical development. [J]. Philos Trans R Soc Lond B Biol Sci, 2012, 367(1607): 3229-3241.