逍遥散治疗郁证大鼠疗效及对犬尿氨酸代谢影响

发布时间：2018-04-11 05:14

  本文选题：逍遥散 + 抑郁症　； 参考：《广州中医药大学》2017年硕士论文

【摘要】：目的:观察逍遥散对慢性轻度不可预知应激诱导的抑郁症模型大鼠行为学、犬尿氨酸代谢产物及海马相关指标的影响,初步探讨逍遥散抗抑郁的作用机制,进一步验证逍遥散的抗抑郁疗效,为抑郁症的诊断和治疗提供客观评价指标,为天然抗抑郁药物奠定理论基础和实验依据。方法:SD雄性大鼠30只,随机分为5个组,健康空白对照组+生理盐水(normal,0.9%NS)、抑郁模型组+生理盐水(model,0.9%NS),模型+帕罗西汀阳性对照组(Paroxetine,10mg/kg),模型+逍遥散水煎剂高剂量组(XYS-high,10.53g/kg)、模型+逍遥散水煎剂低剂量组(XYS-low,5.265 g/kg)。除空白对照组外,其余各组孤养并每日随机给予一到两种刺激,制备慢性不可预见性(CUMS)大鼠模型。造模4 w后给药2 w,在造模的同时给予实验药物,根据大鼠个体体重胃灌相应药量。通过体重、摄食量、强迫游泳实验、旷场实验等指标的测定评估逍遥散对抑郁模型大鼠的影响,于造模前、造模第10、20、28、42 d采集血样,第43 d处死大鼠,快速剥离海马体。采用液相色谱串联质谱法(LC-MS/MS)检测大鼠血浆中色氨酸(TRP)、犬尿氨酸(KYN)、喹啉酸(QUIN)含量的变化;采用实时荧光定量法(Real-time qPCR)考察脑源性神经营养因子(BDNF)、转录因子环磷腺苷反应元件结合蛋白(CREB)及神经细胞黏附分子(NCAM)3种可塑性相关蛋白mRNA表达;采用蛋白质印迹法(Western Blot)考察海马中上述蛋白表达的变化。结果:从行为学结果来看,与正常组相比,CUMS抑郁症大鼠表现出自主活动显著减少,游泳不动时间增加,体重和摄食量下降等,有显著性差异(P0.01);逍遥散治疗后大鼠自主活动、体重和摄食量、游泳不动时间均有所恢复,统计结果有显著性差异(P0.01)。行为学结束后,LC-MS/MS检测结果显示,与正常组相比,第28d模型组大鼠血浆中犬尿氨酸、喹啉酸的浓度降低,有显著性差异(P0.01);逍遥散组与帕罗西汀组治疗后大鼠血浆犬尿氨酸的含量有升高趋势,但无统计学意义(P0.05),逍遥散高剂量组治疗后大鼠血浆喹啉酸的含量明显升高(P0.01)。与正常组相比,模型组大鼠海马中CREB、BDNFmRNA的表达均降低,差异有统计学意义(P0.05),NCAM的蛋白表达显著降低(P0.01);逍遥散高剂量组可使海马组织中的BDNF mRNA表达升高,差异有统计学意义(P0.05)。与正常组相比,模型组大鼠海马组织中NCAM(P0.05)、CREB(P0.01)蛋白表达减少,BDNF无明显差异(P0.05);给药后,与模型组相比,逍遥散组均能使NCAM蛋白表达显著降低,CREB和BDNF蛋白表达显著升高,统计结果有显著性差异(P0.01)。结论:逍遥散对抑郁模型大鼠表现出明显的抗抑郁作用,其调节了犬尿氨酸代谢异常,提高了犬尿氨酸和喹啉酸的含量,并上调了慢性应激抑郁大鼠海马BDNF和CREB的蛋白表达,下调NCAM的蛋白表达,增加BDNF阳性神经元数量,改善神经元形态。逍遥散治疗抑郁症可能是通过改善大鼠犬尿氨酸代谢功能及保护海马神经元作用,但其确切机制如何还有待进一步研究。
[Abstract]:Objective : To observe the effect of Xiaoyao Powder on the behavior , urinary protein metabolism and hippocampus related indexes of depression model induced by chronic mild unpredictable stress . The mechanism of Xiaoyao Powder ' s anti - depression was discussed . It provided an objective evaluation index for the diagnosis and treatment of depression . The model was divided into five groups : normal saline ( normal , 0.9 % NS ) , model + paroxitin positive control group ( group XYS - high , 10.53 g / kg ) , model + Xiaoyao powder decoction dose group ( XYS - low , 5.265 g / kg ) . The results showed that compared with the normal group , there was a significant difference in the levels of urinary and quinoline acids in the plasma of rats . The levels of CREB and BDNFmRNA in the hippocampus of the model group were significantly lower than those in the normal group ( P0.05 ) . Compared with the normal group , the expression of BDNF and CREB in the hippocampus of the model group was significantly lower than that of the normal group ( P0.05 ) . Conclusion : Xiaoyao Powder can significantly decrease the expression of BDNF and CREB in the hippocampus of the rats . The results show that the Xiaoyao Powder can improve the protein expression of BDNF and CREB in the hippocampus of the chronic stress depression rats , increase the number of BDNF positive neurons and improve the neuronal morphology .

【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5
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本文编号：1734579