通络类中药对血管性痴呆大鼠氧化损伤治疗作用机理的实验研究
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摘要
目的:血管性痴呆(Vascular dementia,简称VD)属于老年痴呆病的范畴。近年来,随着社会人口的老龄化,VD患病率呈逐年上升趋势,因其引发的社会问题也越来越引起人们高度的重视。因此,深入探讨VD的发病机制,研发防治VD的药物具有非常重要的意义。本研究通过观察通络类中药对VD大鼠血清中丙二醛(MDA)的含量、一氧化氮(NO)的含量和超氧化物歧化酶(SOD)活性的影响,从抗氧化角度来探讨通络类中药治疗VD的作用机理,为临床治疗VD提供理论依据。
方法
采用反复结扎双侧颈总动脉,同时腹腔注射硝普纳的方法复制VD大鼠模型。将48只健康雌性Wistar大鼠随机分为4组:正常对照组(简称正常组,normal group)、模型组(model group)、尼莫地平对照组(简称对照组,control group)、中药治疗组(简称治疗组,treatment group),12只/组。四组大鼠适应性喂养一周后,对照组、治疗组、模型组行双侧颈总动脉结扎术同时腹腔注射硝普纳复制VD动物模型。正常组不施加任何处理。对照组、治疗组于手术后第二天开始,给予尼莫地平悬浊液及中通络类中药复方制剂的混悬液(水蛭、地龙、僵蚕、土鳖虫)灌胃治疗,正常组和模型组每日给予生理盐水灌胃。各组大鼠均于灌胃两周后断头取血,并分别用硝酸还原酶法测定血清中NO的含量,比色分析法测定血清中的MDA的含量,黄嘌呤及黄嘌呤酶反应法测定血清中SOD的活性。并取右侧脑组织固定后切片,常规HE染色和尼氏染色制作病理切片,在光镜下观察各组大鼠脑组织的形态学变化。
结果
1通络类中药对VD大鼠病理形态学的影响正常组:大鼠大脑皮层神经核团排列整齐,胞体大小正常,核仁明显。
模型组:大鼠皮层神经核团形状极不规则,间质疏松,核固缩成三角形或多角形,胞核染色深或消失,细胞水肿明显。
治疗组:大鼠大脑皮层神经核团排列较整齐,细胞脱失少,仅有少数细胞核固缩成三角形或多角形,细胞水肿不明显。
对照组:大鼠大脑皮层神经核团排列不整齐,细胞脱失较少,有多数细胞核固缩成三角形或多角形,细胞水肿较明显。
2通络类中药对VD大鼠血清中MDA、SOD、NO的影响
2.1通络类中药对VD大鼠血清中MDA含量的影响与正常组比较:各组大鼠血清中MDA的含量均明显增高(P<0.01),且对照组明显高于治疗组(P<0.01)。与模型组比较:治疗组、对照组大鼠血清中MDA的含量均显著下降(P<0.01或P<0.05),且治疗组明显低于对照组(P<0.01)。
2. 2通络类中药对VD大鼠血清中SOD活性的影响
与正常组比较:各组大鼠血清中SOD的含量均明显下降(P<0.01),且对照组明显低于治疗组(P<0.01)。与模型组比较:治疗组、对照组大鼠血清中SOD的含量均明显增高,且治疗组明显高于对照组(P<0.01)。
2. 3通络类中药对VD大鼠血清中NO含量的影响
与正常组比较:各组大鼠血清中NO的含量均显著增高(P<0.01),且对照组明显高于治疗组(P<0.01)。
与模型组比较:治疗组、对照组大鼠血清中NO的含量均显著下降(P<0.01或P<0.05),且治疗组明显低于对照组(P<0.01)。
结论
1通络类中药可明显降低VD大鼠血清中MDA、NO含量,提高SOD的活性,说明通络类中药能明显减轻自由基连锁反应引起的氧化损伤及其对神经功能的迟发性损害。
2通络类中药能够明显改善VD大鼠大脑皮层的损伤。
Objective: Vascular stupid (Vascular dementia, is called VD) to belong to the category which the senile dementia gets sick. In recent years, along with the social population's aging, the VD prevalence rate assumed year by year the trend of escalation, because its initiation's social question also more and more brought to the people high attention. Therefore, discusses VD thoroughly the pathogenesis, the research and development prevents and controls VD the medicine to have the very vital significance. This research passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in the third two baldheaded (MDA) the content, the nitrogen monoxide through the observation (NO) the content and the hyper oxide mutate (SOD) the active influence, discusses from the oxidation resistance angle passes winds a kind of traditional Chinese medicine to treat VD the action mechanism, and provides the theory basis for clinical care VD.
Methods
Uses ties up the two-sided arterial carotids communist anterior repeatedly, simultaneously the abdominal cavity injection niter Punter’s method duplicates the VD big mouse model. Divides into 4 groups stochastically 48 healthy female Wister big mice: The Nimmo horizontal control group (English full title control group), the traditional Chinese medicine treatment group (English full title Traditional Chinese medicine treatment group, called treatment group), the model group (English full title model group), the normal control group (English full title normal control group, called normal group), 12/groups. Four group of big mouse compatibilities feed one week later, the control group, the treatment group, at the same time the model group line two-sided arterial carotids communist anterior legation abdominal cavity injection niter Punier duplicates the VD animal model. The normal group does not exert any processing, the control group, the treatment group after the surgery the second day of start, gives Nepal the money even suspension and passes winds The application of activating collateral drugs compound prescription preparation the suspension (leech, earthworm, dead silkworms, woodlouse) to fill the stomach treatment, the normal group and the model group gives the physiological saline to fill the stomach every day. Each group of big mouse beheads draws blood after two weeks, and uses in separately the nitric acid reductive law determination blood serum the NO content, compares in the color analytic method determination blood serum's MDA content, the xanthenes and in the xanthenes enzyme response law determination blood serum the SOD activeness. After right flank taking the brain organization fixed slices, conventional HE dyes with Nepali dyes the manufacture pathological section, observes the morphological change, which under the light microscope each group of big mouse brain organizes.
Results
1 Passes winds a kind of traditional Chinese medicine to the VD big mouse pathology morphology influence Normal group: Under the light microscope the pathology morphology demonstrated that the big mouse cerebral cortex nerve nuclear group arrange in neat rows, the cell body size is normal, the nucleolus is obvious.
Model group: Under the light microscope the pathology morphology demonstrated that the big mouse cerebral cortex nerve nuclear group shape is extremely anomalous, mesenchymal loose, the karyopyknosis becomes the triangle either the multi-distortions, the nucleus dyeing depth or vanishing, cell dropsy is obvious.
Treatment group: Under the light microscope the pathology morphology demonstrated that the big mouse cerebral cortex nerve nuclear group arranges neatly, the cell escapes lacks, only has the minority cell karyopyknosis to become the triangle or the multi-distortions, cell dropsy is not obvious.
Control group: Under the light microscope the pathology morphology demonstrated that the big mouse cerebral cortex nerve nuclear group arrangement ataxia, the cell escapes loses few, has the most cell karyopyknoses to become the triangle or the multi-distortions, cell dropsy is obvious.
2 Passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in MDA, SOD, the NO influence
2.1 Passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in the MDA influence
Compared with the model group: big mouse blood serum MDA of treatment group and control group content remarkable drop (P <0.01, P <0.05), and the treatment group is lower than the control group obviously (P <0.01).
Compared with treatment group: big mouse blood serum MDA of treatment group and control group content obviously advances(P<0.01),and the control group is higher than the treatment group obviously(P<0.01).
2.2 Passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in the SOD influence
Compared with the model group: big mouse blood serum SOD of treatment group and control group content obvious markup(P<0.01), and the treatment group are higher than the control group obviously(P<0.01).
Compared with treatment group: big mouse blood serum SOD of treatment group and control group content obviously drops(P<0.01), and the control group is lower than the treatment group obviously(P<0.01).
2.3 Passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in the NO influence
Compared with model group: big mouse blood serum NO of treatment group and control group content remarkable drop(P<0.01,P<0.05), and the treatment group is lower than the control group obviously(P<0.01).
Compared with treatment group: big mouse blood serum NO of treatment group and control group content remarkable markup (P<0.01), and the control group is higher than the treatment group(P<0.01).
Conclusion
1 Passes winds a kind of traditional Chinese medicine to be possible to reduce in obviously the VD big mouse blood serum MDA, the NO content, enhances SOD the activeness, explained that passes winds a kind of traditional Chinese medicine to be able to reduce the oxidized damage which and to the nerve function hang fire harm obviously the free radical chain-reaction causes.
2 Passes winds a kind of traditional Chinese medicine to be able to improve the VD big mouse cerebral cortex's damage obviously.
方法
采用反复结扎双侧颈总动脉,同时腹腔注射硝普纳的方法复制VD大鼠模型。将48只健康雌性Wistar大鼠随机分为4组:正常对照组(简称正常组,normal group)、模型组(model group)、尼莫地平对照组(简称对照组,control group)、中药治疗组(简称治疗组,treatment group),12只/组。四组大鼠适应性喂养一周后,对照组、治疗组、模型组行双侧颈总动脉结扎术同时腹腔注射硝普纳复制VD动物模型。正常组不施加任何处理。对照组、治疗组于手术后第二天开始,给予尼莫地平悬浊液及中通络类中药复方制剂的混悬液(水蛭、地龙、僵蚕、土鳖虫)灌胃治疗,正常组和模型组每日给予生理盐水灌胃。各组大鼠均于灌胃两周后断头取血,并分别用硝酸还原酶法测定血清中NO的含量,比色分析法测定血清中的MDA的含量,黄嘌呤及黄嘌呤酶反应法测定血清中SOD的活性。并取右侧脑组织固定后切片,常规HE染色和尼氏染色制作病理切片,在光镜下观察各组大鼠脑组织的形态学变化。
结果
1通络类中药对VD大鼠病理形态学的影响正常组:大鼠大脑皮层神经核团排列整齐,胞体大小正常,核仁明显。
模型组:大鼠皮层神经核团形状极不规则,间质疏松,核固缩成三角形或多角形,胞核染色深或消失,细胞水肿明显。
治疗组:大鼠大脑皮层神经核团排列较整齐,细胞脱失少,仅有少数细胞核固缩成三角形或多角形,细胞水肿不明显。
对照组:大鼠大脑皮层神经核团排列不整齐,细胞脱失较少,有多数细胞核固缩成三角形或多角形,细胞水肿较明显。
2通络类中药对VD大鼠血清中MDA、SOD、NO的影响
2.1通络类中药对VD大鼠血清中MDA含量的影响与正常组比较:各组大鼠血清中MDA的含量均明显增高(P<0.01),且对照组明显高于治疗组(P<0.01)。与模型组比较:治疗组、对照组大鼠血清中MDA的含量均显著下降(P<0.01或P<0.05),且治疗组明显低于对照组(P<0.01)。
2. 2通络类中药对VD大鼠血清中SOD活性的影响
与正常组比较:各组大鼠血清中SOD的含量均明显下降(P<0.01),且对照组明显低于治疗组(P<0.01)。与模型组比较:治疗组、对照组大鼠血清中SOD的含量均明显增高,且治疗组明显高于对照组(P<0.01)。
2. 3通络类中药对VD大鼠血清中NO含量的影响
与正常组比较:各组大鼠血清中NO的含量均显著增高(P<0.01),且对照组明显高于治疗组(P<0.01)。
与模型组比较:治疗组、对照组大鼠血清中NO的含量均显著下降(P<0.01或P<0.05),且治疗组明显低于对照组(P<0.01)。
结论
1通络类中药可明显降低VD大鼠血清中MDA、NO含量,提高SOD的活性,说明通络类中药能明显减轻自由基连锁反应引起的氧化损伤及其对神经功能的迟发性损害。
2通络类中药能够明显改善VD大鼠大脑皮层的损伤。
Objective: Vascular stupid (Vascular dementia, is called VD) to belong to the category which the senile dementia gets sick. In recent years, along with the social population's aging, the VD prevalence rate assumed year by year the trend of escalation, because its initiation's social question also more and more brought to the people high attention. Therefore, discusses VD thoroughly the pathogenesis, the research and development prevents and controls VD the medicine to have the very vital significance. This research passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in the third two baldheaded (MDA) the content, the nitrogen monoxide through the observation (NO) the content and the hyper oxide mutate (SOD) the active influence, discusses from the oxidation resistance angle passes winds a kind of traditional Chinese medicine to treat VD the action mechanism, and provides the theory basis for clinical care VD.
Methods
Uses ties up the two-sided arterial carotids communist anterior repeatedly, simultaneously the abdominal cavity injection niter Punter’s method duplicates the VD big mouse model. Divides into 4 groups stochastically 48 healthy female Wister big mice: The Nimmo horizontal control group (English full title control group), the traditional Chinese medicine treatment group (English full title Traditional Chinese medicine treatment group, called treatment group), the model group (English full title model group), the normal control group (English full title normal control group, called normal group), 12/groups. Four group of big mouse compatibilities feed one week later, the control group, the treatment group, at the same time the model group line two-sided arterial carotids communist anterior legation abdominal cavity injection niter Punier duplicates the VD animal model. The normal group does not exert any processing, the control group, the treatment group after the surgery the second day of start, gives Nepal the money even suspension and passes winds The application of activating collateral drugs compound prescription preparation the suspension (leech, earthworm, dead silkworms, woodlouse) to fill the stomach treatment, the normal group and the model group gives the physiological saline to fill the stomach every day. Each group of big mouse beheads draws blood after two weeks, and uses in separately the nitric acid reductive law determination blood serum the NO content, compares in the color analytic method determination blood serum's MDA content, the xanthenes and in the xanthenes enzyme response law determination blood serum the SOD activeness. After right flank taking the brain organization fixed slices, conventional HE dyes with Nepali dyes the manufacture pathological section, observes the morphological change, which under the light microscope each group of big mouse brain organizes.
Results
1 Passes winds a kind of traditional Chinese medicine to the VD big mouse pathology morphology influence Normal group: Under the light microscope the pathology morphology demonstrated that the big mouse cerebral cortex nerve nuclear group arrange in neat rows, the cell body size is normal, the nucleolus is obvious.
Model group: Under the light microscope the pathology morphology demonstrated that the big mouse cerebral cortex nerve nuclear group shape is extremely anomalous, mesenchymal loose, the karyopyknosis becomes the triangle either the multi-distortions, the nucleus dyeing depth or vanishing, cell dropsy is obvious.
Treatment group: Under the light microscope the pathology morphology demonstrated that the big mouse cerebral cortex nerve nuclear group arranges neatly, the cell escapes lacks, only has the minority cell karyopyknosis to become the triangle or the multi-distortions, cell dropsy is not obvious.
Control group: Under the light microscope the pathology morphology demonstrated that the big mouse cerebral cortex nerve nuclear group arrangement ataxia, the cell escapes loses few, has the most cell karyopyknoses to become the triangle or the multi-distortions, cell dropsy is obvious.
2 Passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in MDA, SOD, the NO influence
2.1 Passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in the MDA influence
Compared with the model group: big mouse blood serum MDA of treatment group and control group content remarkable drop (P <0.01, P <0.05), and the treatment group is lower than the control group obviously (P <0.01).
Compared with treatment group: big mouse blood serum MDA of treatment group and control group content obviously advances(P<0.01),and the control group is higher than the treatment group obviously(P<0.01).
2.2 Passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in the SOD influence
Compared with the model group: big mouse blood serum SOD of treatment group and control group content obvious markup(P<0.01), and the treatment group are higher than the control group obviously(P<0.01).
Compared with treatment group: big mouse blood serum SOD of treatment group and control group content obviously drops(P<0.01), and the control group is lower than the treatment group obviously(P<0.01).
2.3 Passes winds a kind of traditional Chinese medicine to the VD big mouse blood serum in the NO influence
Compared with model group: big mouse blood serum NO of treatment group and control group content remarkable drop(P<0.01,P<0.05), and the treatment group is lower than the control group obviously(P<0.01).
Compared with treatment group: big mouse blood serum NO of treatment group and control group content remarkable markup (P<0.01), and the control group is higher than the treatment group(P<0.01).
Conclusion
1 Passes winds a kind of traditional Chinese medicine to be possible to reduce in obviously the VD big mouse blood serum MDA, the NO content, enhances SOD the activeness, explained that passes winds a kind of traditional Chinese medicine to be able to reduce the oxidized damage which and to the nerve function hang fire harm obviously the free radical chain-reaction causes.
2 Passes winds a kind of traditional Chinese medicine to be able to improve the VD big mouse cerebral cortex's damage obviously.
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