异常黏液质成熟剂颗粒对APP/PS1转基因小鼠行为学和海马组织病理形态学的影响
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摘要
目的观察异常黏液质成熟剂颗粒对APP/PS1转基因小鼠空间学习记忆、海马CA1区组织病理形态学变化的影响,探讨其作用机制。方法选取3月龄APP/PS1转基因模型小鼠并将其随机分为模型组、阳性药组和异常黏液质成熟剂高、中、低剂量组,每组18只。另取18只3月龄C57BL/6J小鼠作为正常组。各给药组给予相应药物灌胃,连续6个月。Morris水迷宫实验观察小鼠学习和记忆能力;HE染色光镜下观察海马CA1区病理形态;透射电镜观察小鼠海马CA1区有髓神经髓鞘、微管、微丝。结果水迷宫实验结果显示,模型组小鼠逃避潜伏期时间较正常组明显延长(P<0.01),空间搜索实验穿越原平台位置次数较正常组明显减少(P<0.01);与模型组比较,异常黏液质成熟剂除低剂量组第1日外其余各剂量组小鼠逃避潜伏期明显缩短(P<0.05,P<0.01),异常黏液质成熟剂低、高剂量组小鼠经过有效区域次数明显增加(P<0.05,P<0.01),异常黏液质成熟剂各剂量组小鼠原平台所在象限停留时间明显增加(P<0.01)。HE染色显示,异常黏液质成熟剂各组小鼠脑组织海马CA1区,锥体细胞层完整性稍好,细胞排列整齐,形态正常,均匀分布;电镜观察,与模型组比较,异常黏液质成熟剂各组小鼠海马CA1区神经元核形不规则,核膜清楚,染色质清晰,核仁明显,细胞基质均匀,细胞器丰富,分布均匀,线粒体嵴明显,粗面内质网和游离核糖体多见。结论异常黏液质成熟剂颗粒可改善APP/PS1转基因小鼠空间学习记忆能力,减轻神经元超微结构受损。
Objective To investigate the effects of Abnormal Phlegmatic Temperament Granules on spatial learning and memory, histopathology morphological change in hippocampus CA1 zone; To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control(donepezil 0.92 mg/kg) group, Abnormal Phlegmatic Temperament Granules high-, medium-,and low-dose groups(3, 2, 1.5 g/kg), 18 mice in each group. Another 18 three-month-old C57BL/ 6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in learning and memory ability of mice were detected by Morris water maze test; pathomorphism in hippocampus CA1 zone was detected by HE staining method; changes of myelin sheath, microtubule, and microfilament in myelinated nerve of hippocampus CA1 zone were detected by electron microscope. Results Morris water maze test results showed that escape incubation period of APP/PS1 transgenic mice was significantly longer than the normal control group(P<0.01), and the original platform time was significantly shorter than normal control group(P<0.01); compared with model control group, Abnormal Phlegmatic Temperament Granules treatment groups escape latency time was significantly reduced(P<0.05, P<0.01). Space experiments and escape incubation period of Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups were significantly shortened(P<0.05,P<0.01), and spatial searching test showed that the times of mice in Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups passing through effective area increased(P<0.01). The integrity of HE staining pyramidal cell layer in the hippocampus CA1 zones of Abnormal Phlegmatic Temperament Granules high-, medium-,and low-dose groups was relatively good; cells arranged orderly; distribution was normal. Electron microscopic observation showed that compared with model control group, the hippocampus neurons nuclear had irregular shape;nuclear membrane was clear and complete; chromatin was clear; nucleolus was obvious; cell matrix was uniform;organelles were abundant; mitochondrial cristae was obvious; endoplasmic reticulum and free ribosomes were obvious. Conclusion Abnormal Phlegmatic Temperament Granules can improve spatial learning and memory in APP/PS1 mice, alleviate neuronal ultrastructure damage and ultimately improve cognitive function.
Objective To investigate the effects of Abnormal Phlegmatic Temperament Granules on spatial learning and memory, histopathology morphological change in hippocampus CA1 zone; To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control(donepezil 0.92 mg/kg) group, Abnormal Phlegmatic Temperament Granules high-, medium-,and low-dose groups(3, 2, 1.5 g/kg), 18 mice in each group. Another 18 three-month-old C57BL/ 6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in learning and memory ability of mice were detected by Morris water maze test; pathomorphism in hippocampus CA1 zone was detected by HE staining method; changes of myelin sheath, microtubule, and microfilament in myelinated nerve of hippocampus CA1 zone were detected by electron microscope. Results Morris water maze test results showed that escape incubation period of APP/PS1 transgenic mice was significantly longer than the normal control group(P<0.01), and the original platform time was significantly shorter than normal control group(P<0.01); compared with model control group, Abnormal Phlegmatic Temperament Granules treatment groups escape latency time was significantly reduced(P<0.05, P<0.01). Space experiments and escape incubation period of Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups were significantly shortened(P<0.05,P<0.01), and spatial searching test showed that the times of mice in Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups passing through effective area increased(P<0.01). The integrity of HE staining pyramidal cell layer in the hippocampus CA1 zones of Abnormal Phlegmatic Temperament Granules high-, medium-,and low-dose groups was relatively good; cells arranged orderly; distribution was normal. Electron microscopic observation showed that compared with model control group, the hippocampus neurons nuclear had irregular shape;nuclear membrane was clear and complete; chromatin was clear; nucleolus was obvious; cell matrix was uniform;organelles were abundant; mitochondrial cristae was obvious; endoplasmic reticulum and free ribosomes were obvious. Conclusion Abnormal Phlegmatic Temperament Granules can improve spatial learning and memory in APP/PS1 mice, alleviate neuronal ultrastructure damage and ultimately improve cognitive function.
引文
[1]新疆维吾尔自治区卫生厅中国医学百科全书维吾尔医分卷办公室.中国医学百科全书:维吾尔医学分卷[M].乌鲁木齐:新疆人民卫生出版社,1985:17-25.
[2]MORRIS R.Developments of a water-maze procedure for studying spatial learning in the rat[J].J Neurosci Methods,1984,11(1):47-60.
[3]帕丽丹·吾术尔,买吾拉尼江·依孜布拉,努尔买买提·艾买提,等.阿尔茨海默病异常黑胆质病证结合大鼠模型血清代谢组学研究[J].科技导报,2014,32(28/29):39-47.
[4]邱昕,陈国华,冯佩,等.黄连解毒汤对APP/PS1双转基因AD小鼠海马区病理形态学及脑内t B-APP基因表达的影响[J].神经损伤与功能重建,2010,5(6):404-408.
[5]哈木拉提·吾甫尔,党明,热娜古丽·艾则孜,等.异黑颗粒对APP/PS1双转基因模型小鼠学习记忆和抗氧化能力的影响[J].科技导报,2013,31(14):26-29.
[6]OANA C,Lucian H,Marius M,et al.Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloidβ(1–42)rat model of Alzheimer's disease[J].Physiology&Behavior,2013,120(15):193-202.
[2]MORRIS R.Developments of a water-maze procedure for studying spatial learning in the rat[J].J Neurosci Methods,1984,11(1):47-60.
[3]帕丽丹·吾术尔,买吾拉尼江·依孜布拉,努尔买买提·艾买提,等.阿尔茨海默病异常黑胆质病证结合大鼠模型血清代谢组学研究[J].科技导报,2014,32(28/29):39-47.
[4]邱昕,陈国华,冯佩,等.黄连解毒汤对APP/PS1双转基因AD小鼠海马区病理形态学及脑内t B-APP基因表达的影响[J].神经损伤与功能重建,2010,5(6):404-408.
[5]哈木拉提·吾甫尔,党明,热娜古丽·艾则孜,等.异黑颗粒对APP/PS1双转基因模型小鼠学习记忆和抗氧化能力的影响[J].科技导报,2013,31(14):26-29.
[6]OANA C,Lucian H,Marius M,et al.Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloidβ(1–42)rat model of Alzheimer's disease[J].Physiology&Behavior,2013,120(15):193-202.