补元聪脑汤对老年性痴呆大鼠行为学及海马神经元细胞凋亡的干预作用
摘要
目的:本论文旨在探讨老年性痴呆肾气亏虚为本、痰瘀阻络为标的发病机制,并通过建立老年性痴呆大鼠多因素复合模型,从行为学及海马区神经元细胞凋亡的角度观察补元聪脑汤对老年性痴呆的干预效果及作用机理。
方法:本实验采用鹅膏蕈氨酸(IBO)+β淀粉样蛋白1-42等量复合注射液法复制AD大鼠模型,以补元聪脑汤进行中药干预,并设西药脑复康(吡拉西坦片)为对照。通过Morris水迷宫法测试大鼠主动和被动的学习记忆能力。光镜下观察脑海马区病理形态变化。细胞免疫组织化学法测定海马区bax、bcl-2蛋白水平的表达。
结果:
1.行为学:模型组与正常组比较逃避潜伏期明显延长、跨越平台的次数明显减少(P均<0.01);中药组、西药组与模型组比较逃避潜伏期缩短,跨越平台次数增多(P均<0.01)。无论是中药还是西药,治疗均有效。而中药治疗与西药治疗的效果相近,并没有显著差异(P均>0.05)。
2.细胞凋亡:模型组与正常组比较,bax蛋白表达明显升高,bcl-2明显降低(P均<0.01);中药组、西药组与模型组比较bax蛋白表达水平下降,bcl-2则上升(P均<0.01)。中药组与西药组间无显著性差异(P均>0.05)。
3.形态学改变:模型组神经元数目比正常组明显减少,阳性神经元数目明显增多,可见部分神经元细胞核有固缩状态,核膜增厚、畸变,甚至神经元变性坏死,胞脂褐素增多等细胞凋亡现象。中药组与西药组均使阳性神经元数目降低,神经纤维分布较模型组规整。
结论:
1.肾亏痰瘀阻络是老年性痴呆的基本病机之一,补肾开瘀涤痰是其有效治则。
2.多因素复合模型(IBO+Aβ1-42)能有效地模拟老年性痴呆的行为学及病理学特征,是一种及其可靠的动物模型。
3.补元聪脑汤能明显降低AD大鼠海马区神经元bax阳性细胞数,升高bcl-2阳性细胞数,抑制AD大鼠海马神经元细胞凋亡。
4.补元聪脑汤对AD大鼠脑神经元细胞的保护作用可能是通过增强受损海马区神经元bcl-2蛋白的表达,并减少bax蛋白的表达。从而改善AD大鼠的学习记忆能力。
Purpose:Exploration on pathogenic mechanism of kidney-Qi deficiency and phlegm stasis in Alzheimer’s disease by establishing the muti-factor compound rat model of Alzheimer’s disease(AD), to explore the interference and therapeutic mechanism of Buyuan Congnao Decoction (BCD) in treating AD from behaviology and nerve cells apoptosis.
method:To adopt IBO and Aβ1-42 of the mixed solution inject to sea horse area establish AD rat models. Carrying on Chinese medicine intervention by BCD, and taking Piracetam-NEGPF as to be the checking-medicine. And apply Morris water maze method to examine memory abilities of study on initiative and passive on AD rat models. Observed pathological morphology of hippocampus by the light microscope. The expression of apoptosis related protein Bax and Bcl-2 in rats’hippocampus were studied by immunohistochemistry method.
Results:
1. Ethology: compared with normal group, latency period of escape in model group prolonged obviously, frequency of finding the platform decreased, number of times of mistake increased(P<0.01). Treat group compared with model group, latency period of escape shortened, frequency of finding the platform increased, number of times of mistake decreased (P<0.01). Regardless of Chinese medicine and Western medicine, both of them are available. And the treatment of Chinese medicine and Western medicine contains close, to say in other words, they are no distinguish differences(P>0.05).
2. Apoptosis: compared with normal group, protein level of bax ascended, bcl-2 descended (P<0.01). Treat group compared with model group, protein level of bax descended, and bcl-2 ascended (P<0.01). no matter what Chinese medicine and Western medicine are no conspicuous differences (P>0.05).
3. Morphology change: number of neuron of model group was less than that of normal group, and sum of pathologic neuron was more than that of normal group. Cell apoptosis phenomenon could be seen, such as cell nucleus of some neuron showed pyknosis condition, caryotheca thicked and aberration, degeneration, necrosis, lipofuscin increased and so on. Both of BCD treat group and checking-medcine can decreased number of pathologic neuron, Compared with model group, distribution of neurofibra was more regular.
Conclusion:
1. Kidney deficiency and phlegm stasis is the basic etiological factor for AD, and replenishing kidney and removing phlegm stasis therapy is active on treating AD.
2. The animal model of Alzheimer’s disease induced by composite Aβ1-42 and IBO injected into basal nucleus of Meynert of rats simulated some characteristics and pathology of human AD to some extent, which may used as a reliable model to study AD.
3. Buyuan Congnao Decoction (BCD) could decrease the expression of bax of hippocampus neural cells of rats, and increase the expression of bcl-2, and suppress the apoptosis of hippocampus neural cells of rats.
4. The protection function of Buyuan Congnao Decoction (BCD) which to the AD rats’brain nerve cells is possible that strengthen expression to damaged hippocampus neuron bcl-2, and decrease to bax .Thus the study and memory of the AD rat is improved.
方法:本实验采用鹅膏蕈氨酸(IBO)+β淀粉样蛋白1-42等量复合注射液法复制AD大鼠模型,以补元聪脑汤进行中药干预,并设西药脑复康(吡拉西坦片)为对照。通过Morris水迷宫法测试大鼠主动和被动的学习记忆能力。光镜下观察脑海马区病理形态变化。细胞免疫组织化学法测定海马区bax、bcl-2蛋白水平的表达。
结果:
1.行为学:模型组与正常组比较逃避潜伏期明显延长、跨越平台的次数明显减少(P均<0.01);中药组、西药组与模型组比较逃避潜伏期缩短,跨越平台次数增多(P均<0.01)。无论是中药还是西药,治疗均有效。而中药治疗与西药治疗的效果相近,并没有显著差异(P均>0.05)。
2.细胞凋亡:模型组与正常组比较,bax蛋白表达明显升高,bcl-2明显降低(P均<0.01);中药组、西药组与模型组比较bax蛋白表达水平下降,bcl-2则上升(P均<0.01)。中药组与西药组间无显著性差异(P均>0.05)。
3.形态学改变:模型组神经元数目比正常组明显减少,阳性神经元数目明显增多,可见部分神经元细胞核有固缩状态,核膜增厚、畸变,甚至神经元变性坏死,胞脂褐素增多等细胞凋亡现象。中药组与西药组均使阳性神经元数目降低,神经纤维分布较模型组规整。
结论:
1.肾亏痰瘀阻络是老年性痴呆的基本病机之一,补肾开瘀涤痰是其有效治则。
2.多因素复合模型(IBO+Aβ1-42)能有效地模拟老年性痴呆的行为学及病理学特征,是一种及其可靠的动物模型。
3.补元聪脑汤能明显降低AD大鼠海马区神经元bax阳性细胞数,升高bcl-2阳性细胞数,抑制AD大鼠海马神经元细胞凋亡。
4.补元聪脑汤对AD大鼠脑神经元细胞的保护作用可能是通过增强受损海马区神经元bcl-2蛋白的表达,并减少bax蛋白的表达。从而改善AD大鼠的学习记忆能力。
Purpose:Exploration on pathogenic mechanism of kidney-Qi deficiency and phlegm stasis in Alzheimer’s disease by establishing the muti-factor compound rat model of Alzheimer’s disease(AD), to explore the interference and therapeutic mechanism of Buyuan Congnao Decoction (BCD) in treating AD from behaviology and nerve cells apoptosis.
method:To adopt IBO and Aβ1-42 of the mixed solution inject to sea horse area establish AD rat models. Carrying on Chinese medicine intervention by BCD, and taking Piracetam-NEGPF as to be the checking-medicine. And apply Morris water maze method to examine memory abilities of study on initiative and passive on AD rat models. Observed pathological morphology of hippocampus by the light microscope. The expression of apoptosis related protein Bax and Bcl-2 in rats’hippocampus were studied by immunohistochemistry method.
Results:
1. Ethology: compared with normal group, latency period of escape in model group prolonged obviously, frequency of finding the platform decreased, number of times of mistake increased(P<0.01). Treat group compared with model group, latency period of escape shortened, frequency of finding the platform increased, number of times of mistake decreased (P<0.01). Regardless of Chinese medicine and Western medicine, both of them are available. And the treatment of Chinese medicine and Western medicine contains close, to say in other words, they are no distinguish differences(P>0.05).
2. Apoptosis: compared with normal group, protein level of bax ascended, bcl-2 descended (P<0.01). Treat group compared with model group, protein level of bax descended, and bcl-2 ascended (P<0.01). no matter what Chinese medicine and Western medicine are no conspicuous differences (P>0.05).
3. Morphology change: number of neuron of model group was less than that of normal group, and sum of pathologic neuron was more than that of normal group. Cell apoptosis phenomenon could be seen, such as cell nucleus of some neuron showed pyknosis condition, caryotheca thicked and aberration, degeneration, necrosis, lipofuscin increased and so on. Both of BCD treat group and checking-medcine can decreased number of pathologic neuron, Compared with model group, distribution of neurofibra was more regular.
Conclusion:
1. Kidney deficiency and phlegm stasis is the basic etiological factor for AD, and replenishing kidney and removing phlegm stasis therapy is active on treating AD.
2. The animal model of Alzheimer’s disease induced by composite Aβ1-42 and IBO injected into basal nucleus of Meynert of rats simulated some characteristics and pathology of human AD to some extent, which may used as a reliable model to study AD.
3. Buyuan Congnao Decoction (BCD) could decrease the expression of bax of hippocampus neural cells of rats, and increase the expression of bcl-2, and suppress the apoptosis of hippocampus neural cells of rats.
4. The protection function of Buyuan Congnao Decoction (BCD) which to the AD rats’brain nerve cells is possible that strengthen expression to damaged hippocampus neuron bcl-2, and decrease to bax .Thus the study and memory of the AD rat is improved.
引文
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