自拟健脾益气方药的抗抑郁作用及其机制研究
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摘要
目的 探讨自拟健脾益气方药(SMP-SSRQ)的抗抑郁作用及其机制。方法 建立慢性不可预知性温和应激(chronic unpredictable mild stress,CUMS)抑郁小鼠模型,随机分为正常组、模型组、SMP-SSRQ低、中、高剂量组(8、16、32 mg·kg~(-1)),每组12只。正常对照组与模型组动物给予同体积的生理盐水,SMP-SSRQ各剂量组分别给予相应剂量的药物。均采用灌胃给药,每天2次,连续给药2周。通过旷场、糖水消耗、强迫游泳和悬尾等实验检测动物的不同行为学指标;采用实时荧光定量PCR和Western blot分别检测各组小鼠大脑前额叶皮质和海马组织中免疫球蛋白超家族11(Igsf11)、蛋白质二硫键异构酶2(Pdia2)、生育酚结合蛋白(Sec14l2)mRNA及蛋白水平的表达变化。结果 与模型组比较,SMP-SSRQ各治疗组均可增加抑郁小鼠的水平移动格数、直立次数以及糖水偏好指数(P<0.05),降低强迫游泳和悬尾不动时间,明显改善抑郁症状;低、高剂量的SMPSSRQ能明显降低抑郁小鼠大脑皮层前额叶与海马组织中Igsf11、Pdia2、Sec14l2 mRNA及蛋白的表达水平,与模型组比较差异有显著性(P<0.05)。结论 SMP-SSRQ可有效改善小鼠的抑郁行为,机制可能与其下调小鼠皮层和海马组织中的Igsf11、Pdia2、Sec14l2的mRNA及其蛋白水平有关。
Aim To explore the antidepressant effect and the mechanism of self-made prescription of strengthening spleen and replenishing Qi(SMP-SSRQ). Methods The depression model of chronic unpredictable mild stress(CUMS) was established in mice. The animals were randomly divided into control group,model group,SMP-SSRQ low,middle and high dose groups(8,16,32 mg·kg~(-1)),with 12 mice for each group. The control group and the model group were given the same volume of saline,and other groups were given corresponding dose of SMP-SSRQ. Animals of each group were administered by gavage twice a day for two weeks. Behavioral indexes of mice were determined by open field experiment,sugar consumption test,forced swimming test and tail suspension test.Quantitative real-time PCR(q PCR) and Western blot were respectively performed to detect mRNA and protein expression levels of Igsf11,Pdia2 and Sec14l2 in prefrontal cortex and hippocampus. Results Compared with model group,depressed mice's horizontal mobile score,upright number and the sugar water preference index increased and FST as well as TST decreased in all SMP-SSRQ groups(P < 0. 05). The depression symptoms in mice were obviously improved by SMP-SSRQ therapy. Low and high doses of SMP-SSRQ significantly reduced mRNA and protein expression level of Igsf11,Pdia2 and Sec14l2 in the prefrontal cortex and hippocampus of the depressed mice,presenting significant statistical difference compared with model group(P < 0. 05). Conclusions SMP-SSRQ can effectively improve mouse depressive behavior,and its mechanism may be related to the down-regulation of Igsf11,Pdia2 and Sec14l2 in mouse prefrontal cortex and hippocampus.
Aim To explore the antidepressant effect and the mechanism of self-made prescription of strengthening spleen and replenishing Qi(SMP-SSRQ). Methods The depression model of chronic unpredictable mild stress(CUMS) was established in mice. The animals were randomly divided into control group,model group,SMP-SSRQ low,middle and high dose groups(8,16,32 mg·kg~(-1)),with 12 mice for each group. The control group and the model group were given the same volume of saline,and other groups were given corresponding dose of SMP-SSRQ. Animals of each group were administered by gavage twice a day for two weeks. Behavioral indexes of mice were determined by open field experiment,sugar consumption test,forced swimming test and tail suspension test.Quantitative real-time PCR(q PCR) and Western blot were respectively performed to detect mRNA and protein expression levels of Igsf11,Pdia2 and Sec14l2 in prefrontal cortex and hippocampus. Results Compared with model group,depressed mice's horizontal mobile score,upright number and the sugar water preference index increased and FST as well as TST decreased in all SMP-SSRQ groups(P < 0. 05). The depression symptoms in mice were obviously improved by SMP-SSRQ therapy. Low and high doses of SMP-SSRQ significantly reduced mRNA and protein expression level of Igsf11,Pdia2 and Sec14l2 in the prefrontal cortex and hippocampus of the depressed mice,presenting significant statistical difference compared with model group(P < 0. 05). Conclusions SMP-SSRQ can effectively improve mouse depressive behavior,and its mechanism may be related to the down-regulation of Igsf11,Pdia2 and Sec14l2 in mouse prefrontal cortex and hippocampus.
引文
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[2]Zhu Y,Chao C,Duan X,et al.Kai-Xin-San series formulae alleviate depressive-like behaviors on chronic mild stressed mice via regulating neurotrophic factor system on hippocampus[J].Sci Rep,2017,7(1):1467.
[3]司天梅,于欣.目前研究和开发更有效的抗抑郁药过程中存在的问题[J].上海精神医学,2016,28(3):160-5.[3]Si T M,Yu X.Current problems in the research and development of more effective antidepressants[J].Shanghai Arch Psychiatry,2016,28(3):160-5.
[4]Zhang K,Yang J,Wang F,et al.Antidepressant-like effects of Xiaochaihutang in a neuro endocrine mouse model of anxiety/depression[J].J Ethnopharmacol,2016,194:674-83.
[5]Wang C,Guo J,Guo R.Effect of Xing Pi Jie Yu decoction on spatial learning and memory and c AMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress[J].BMC Complement Altern Med,2017,17(1):73.
[6]Zhan H,Huang F,Yan F,et al.Alterations in splenic function and gene expression in mice with depressive-like behavior induced by exposure to corticosterone[J].Int J Mol Med,2017,39(2):327-36.
[7]Jang S,Oh D,Lee Y,et al.Synaptic adhesion molecule Ig SF11regulates synaptic transmission and plasticity[J].Nat Neurosci,2016,19(1):84-93.
[8]Halloran M,Parakh S,Atkin J D.The role of s-nitrosylation and s-glutathionylation of protein disulphide isomerase in protein misfolding and neurodegeneration[J].Int J Cell Biol,2013,18:797914.
[9]张海娜,徐慧,余旭奔,等.辛伐他汀对脂多糖诱导的小鼠抑郁行为及神经炎症的影响[J].中国药理学通报,2017,33(3):373-8.[9]Zhang H N,Xu H,Yu X B,et al.Effect of simvastatin on lipopolysaccharides induced depressive behaviors and neuroinflammation in mice[J].Chin Pharmacol Bull,2017,33(3):373-8.
[10]刘会茹.JPYQ现代方药和Euparin抗抑郁作用及其机制研究[D].新乡:新乡医学院,2017.[10]Liu H R.The study of JPYQ modern compound and Euparin on the anti-depressant effects and its mechanism[D].Xinxiang:Xinxiang Medical University,2017.
[11]Liu C,Wang J,Xu S,et al.Paecilomyces tenuipes extract prevents depression-like behaviors in chronic unpredictable mild stress-induced rat model via modulation of neurotransmitters[J].Mo L Med Rep,2017,16(2):2172-8.
[12]Malkov A,Lvanov A I,Popova I,et al.Reactive oxygen species initiate a metabolic collapse in hippocampal slices:potential trigger of cortical spreading depression[J].J Cereb Blood Flow Metab,2014,34(9):1540-9.
[13]Zhou X Y,Zhang F,Ying C J,et al.Inhibition of i NOS alleviates cognitive deficits and depression in diabetic mice through downregulating the NO/s GC/c GMP/PKG signal pathway[J].Behav Brain Res,2017,322(Pt A):70-82.
[14]Rebai R,Jasmin L,Boudah A.The antidepressant effect of melatonin and fluoxetine in diabetic rats is associated with a reduction of the oxidative stress in the prefrontal and hippocampal cortices[J].Brain Res Bull,2017,134:142-50.
[15]Lian Y J,Gong H,Wu T Y,et al.Ds-HMGB1 and fr-HMGB induce depressive behavior through neuroinflammation in contrast to nonoxid-HMGB1[J].Brain Behav Immun,2017,59:322-32.