从痰论治痴呆及石菖蒲对拟AD大鼠模型的作用及机制研究

发布时间：2018-06-05 12:29

本文选题：老年性痴呆 + 痰蒙脑窍　；参考：《湖北中医药大学》2017年硕士论文

【摘要】：目的从痰浊角度探讨老年性痴呆(AD)的发病机理和治疗法则,并通过观察石菖蒲及其挥发油成分对AD模型大鼠学习记忆水平、胆碱能系统功能、神经生长因子水平和神经细胞凋亡的影响,探讨石菖蒲对AD模型的干预作用及物质基础,为中医药防治AD提供实验依据。方法Wistar大鼠70只,随机分为7组,即正常组、假手术组、模型组、多奈哌齐组(0.33mg kg-1 d-1)、石菖蒲水煎液组(20mg kg-1 d-1)、石菖蒲挥发油组(20mg kg-1 d-1)、β-细辛醚组(25 mgkg-1 d-1),每组10只。大鼠海马注射Aβ1-42构建拟AD大鼠模型,各组大鼠均按1ml/100g·d灌胃给药,连续28d。采用Morris水迷宫实验观察实验大鼠学习记忆能力,放射免疫法检测大鼠海马Ach、AchE和ChAT活性变化,ELISA法检测海马组织NGF含量,流式细胞仪检测神经细胞凋亡率。结果1.历时5天的定位航行实验中,各组大鼠的逃避潜伏期总体呈下降趋势,前2天各组间没有显著差异。第3天,模型组大鼠的逃避潜伏期与正常组相比明显延长(P0. 05),石菖蒲挥发油组、多奈哌齐组和β-细辛醚组与模型组比有显著差异(P0. 05);第4天,多奈哌齐组、石菖蒲挥发油组、β-细辛醚组与模型组相比逃避潜伏期显著缩短(P0.01);第5天,各用药组与模型组相比逃避潜伏期显著缩短(P0.01 )。2.第6天空间探索实验结果显示,模型组目标象限游泳时间占整个游泳时间的百分比与正常组相比明显缩短,空间搜索能力显著下降(P0.01)。多奈哌齐组、石菖蒲水煎液组、石菖蒲挥发油组、β-细辛醚组与模型组相比平台象限比显著增长(P 0.01),其中石菖蒲挥发油组已接近正常水平(P0. 05)。各组大鼠在跨过原平台位置次数结果显示,模型组较其它各组大鼠跨过原平台位置次数明显下降(P0.01)。多奈哌齐组、石菖蒲水煎液组、石菖蒲挥发油组、β-细辛醚组与模型组比跨过原平台位置次数显著增多(P0. 01 )。3.模型组海马组织Ach和ChAT与正常组相比均显著减少(P0. 01),AchE活性则明显升高(P0.01)。与模型组比,各治疗组Ach和ChAT结果显著升高,均有显著性差异(P0. 01),与多奈哌齐组比较,石菖蒲水煎液组Ach和ChAT活性有显著差异(P0. 05)。与模型组比,各治疗组AchE含量显著降低,均有显著性差异(P0. 01),与多奈哌齐组比较,石菖蒲水煎液组和β -细辛醚组AchE活性有显著差异(P0. 05,P0.01 )。4.海马组织NGF含量结果表明,模型组NGF含量明显降低(P0.01)。各治疗组NGF含量结果显著升高,均有显著性差异(P0. 01)。与多奈哌齐组比较,石菖蒲水煎液组、石菖蒲挥发油组和β-细辛醚组NGF含量有显著差异(P0. 05, P0.01 )。5.流式细胞术检测大鼠海马神经细胞凋亡实验发现,模型组神经细胞G1峰左侧出现亚二倍体细胞群的峰型。各治疗组亚2倍体峰均有一定程度上出现。模型组海马组织神经细胞凋亡率与正常组相比均显著增高(P0. 01)。与模型组比,各治疗组神经细胞凋亡率显著降低,均有显著性差异(P0.01),与多奈哌齐组比较,石菖蒲水煎液组、石菖蒲挥发油组和β-细辛醚组神经细胞凋亡率有显著差异(P0. 05, P0. 01 )。结论1.痰浊困阻,蒙蔽脑窍为老年性痴呆发病的重要因素,化痰开窍醒神益智是痴呆治疗的重要法则。2.无论从反映空间学习记忆获取能力的定位航行试验,还是从反映信息贮存能力的空间搜索实验来看,治疗各组能有效地改善实验大鼠的学习行为能力。其中石菖蒲挥发油组效果最好,其次顺序依次为多奈哌齐组、β-细辛醚组、石菖蒲水煎液组。3.石菖蒲及提取物对中枢胆碱能损害具有修复作用,能增加海马组织内源性NGF含量,抑制脑神经细胞凋亡,其中均以石菖蒲挥发油组效果最佳。4.石菖蒲及其提取物能有效改善模型大鼠受损的学习记忆水平,其作用机制可能是通过提高内源性NGF含量,从而抑制凋亡程序的发生,促进去神经支配区的胆碱能纤维数量增加,这有助于神经元损伤后功能的迅速恢复,从而达到改善学习记忆的作用。
[Abstract]:Objective To study the pathogenesis and therapeutic principles of AD in rats . The effects of Rhizoma Acori Tatarinowii and its volatile oil on learning and memory level , cholinergic system function , nerve growth factor level and neuronal apoptosis in AD rats were studied . Compared with the model group , the swimming time of the target quadrant of the model group was significantly shorter than that of the model group ( P0.01 ) . The results of the sixth day space exploration experiment showed that the swimming time of the target quadrant of the model group was significantly shorter than that in the normal group ( P0.01 ) . Compared with the normal group , there was a significant difference in the activity of AchE ( P0.01 ) . Compared with the model group , there was a significant difference in the activity of AchE and ChAT in the model group ( P0.01 ) . Compared with the model group , there was a significant difference in the activity of AchE and ChAT in the model group ( P0.01 ) . The content of NGF in hippocampus was significantly lower than that in model group ( P0.05 , P0.01 ) . The content of NGF in hippocampus was significantly decreased ( P0.01 ) . The content of NGF in hippocampus of the model group was higher than that in the normal group ( P0.01 ) . Compared with the model group , the apoptosis rate of nerve cells in each treatment group was significantly decreased ( P0.01 ) . Conclusion 1 . The effect of Rhizoma Acori Tatarinowii and its extract can improve the learning and memory level of experimental rats .
【学位授予单位】：湖北中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5;R-332

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