电项针对脑出血大鼠脑水肿与细胞凋亡调控因素的影响
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摘要
目的:通过电项针对脑出血大鼠模型影响的实验研究,探讨电项针对脑出血后脑水肿和细胞凋亡调控因素影响的机制。
方法:本实验用健康雄性(wistar)大鼠144只,体重250-300克,按随机数字表分为A、B、C三组,每组又各分为12h、24h、3d、7d四个小组。每小组每时间点各12只动物。动物经10%水合氯醛腹腔麻醉(400mg/kg体重),头顶备皮后将动物固定于三维立体定位仪上,局部皮肤处理后以前囱为坐标原点,向大鼠尾侧0.2mm,大鼠右侧2.9mm,确定注射点坐标,用牙科钻钻孔约直径1.0mm(在右尾状核位置),A组(对照组)注入2ul0.9%的生理盐水,B组(模型组)C组(电项针组)均用微量注射器吸取含0.5u/ul胶原酶的生理盐水和7u/ul肝素的生理盐水各1.0ul注入,每组于注射完毕退出针后,缝合头皮,并于12h、24h、3d、7d参照Longa FZ五级评分法进行神经功能学评分,评分完毕后,按要求处置,测定脑含水量,及脑组织形态学观察,超微结构改变及免疫组化方法观察AQP-4,MMP-9,Caspase-3和Bcl-2蛋白的表达。
结果:
1、脑出血后大鼠出现神经功能缺损,3d达高峰,之后有所下降。电项针组与模型组比较差异显著(P＜0.05)。电项针组可以降低神经功能缺损程度。
2、脑出血大鼠模型24h后脑含水量明显增高,3d达高峰,电项针组有较明显的抗脑水肿作用,各时间点比较有统计学意义(P＜0.05)。
3、HE染色显示:脑出血后24h血肿周围可见白细胞浸润,细胞间隙和血管周围间隙增宽,3d上述病变加重,并见大量神经细胞变性坏死,7d仍有增生的胶质细胞,从病变的程度和范围看,电项针组的病理改变要轻于模型组。
4、电镜观察电项针组神经细胞超微结构的变化明显改善;与模型组比较电项针组神经元细胞内,可见高尔基,线粒体和其他细胞器结构完整,突触膜活性区,突触小泡增多。
5、AQP-4表达;模型组中3d达高峰,各时点均显著高于对照组;电项针组的表达显著低于模型组(P＜0.01)。
6、MMP-9表达;模型组3d达高峰,各时点均显著高于对照组;电项针组的表达显著低于模型组(P＜0.01)。
7、Caspase-3表达;模型组24小时达高峰,各时点均显著高于对照组;电项针组的表达显著低于模型组(P＜0.01)。
8、Bcl-2表达;模型组24小时达高峰,各时点均高于对照组;电项针组的表达显著高于模型组(P＜0.01)。
结论:
1、电项针能明显降低脑出血大鼠模型神经功能缺损评分,促进神经功能恢复。
2、通过血肿周围脑组织形态学,血脑屏障超微结构,脑组织水肿带超微结构的观察与对比,电项针刺能够有效调整微观组织结构的病理改变程度。
3、大鼠脑出血后AQP-4与MMP-9的释放与激活,是脑出血后早中期脑水肿形成的重要因素之一,导致BBB通透性增加而造成脑水含量增加。
4、大鼠脑出血后Caspase-3与Bcl-2的释放与激活,是脑出血后脑细胞凋亡相关的重要因素。
5、电项针治疗具有抗脑出血后脑水肿的作用及减轻脑细胞凋亡的作用,机制之一是对AQP-4,MMP-9,Caspase-3表达的抑制,Bcl-2表达的增加,使BBB开放程度减小,降低脑组织含水量,减轻脑水肿程度及保护神经细胞。
Objective:To research the mechanism of control factor in which electro-nape acupuncture therapy influences the brain edema and apoptosis occurred from intracerebral hemorrhage,through the experiment on the rats with intracerebral hemorrhage.
Method:healthy male wistar rats(weight:250-300g) were randomly divided into three groups:A,B and C,each group was again randomly divided into four smaller groups;12h、24h、3d、7d four time points,the rats were prepared by rules.The rats in group A were injected 0.9%physiological saline 2ul,the rats in group B and C were injected 0.9% physiological saline with 0.5u/ul collagenase 1ul and 0.9%physiological saline with 7u/ul heparin 1ul,then observe the information and data at assigned time:Neurological deficit scale,the brain tissue water content,braintissue patho-form,braintissue ultramicro-texture and AQP-4,MMP-9,Caspase-3 and Bcl-2 by immunity histochemistry method.
Results:
1.the recordings indicate there is Neurological deficit scale in hemorrhage rats,the peak occurred at 3d and descent then.There are significant disparity between model group and treating group.
2.The brain tissue water content step up after 24h and the peak occurred at 3d,there are significant disparity between model group and treating group.
3.Light-microscope shows there's severe pathological change in brain hemorrhagic model group,Nerve cells and colloidal cells swell,and in cell space there's vacuoles of different sizes and the cell space increases.In treating group,hemorrhage and cell dropsy are distinctly alleviated.
4.Electron microscope results show that the cerebral ultrastructure was significantly meliorated in treating group;There were plenty of golgicomplexes in neuron,the structure of mitochondrion and other cell organs were full and there were more synaptic vesicles in treating group.
5.The AQP-4 expression in model group reach peak at 3d,there are significant disparity between model group and treating group(P＜0.01).
6.The MMP-9 expression in model group reach peak at 3d,there are significant disparity between model group and treating group(P＜0.01)
7.The Caspase-3 expression in model group reach peak at 24h,there are significant disparity between model group and treating group(P＜0.01)
8.The Bcl-2 expression in model group reach peak at 24h,there are significant disparity between model group and treating group(P＜0.01)
Conclusion:
1.Electro-nape acupuncture therapy reduces Neurological deficit scale in hemorrhagerats,improves the nervous function.
2.Through observing and comparing braintissue morphology around hematoma,BBB ultramicro-texture,ultramicro-texture of braintissue-edema zone,Electro-nape acupuncture therapy improves pathological change of braintissue-ultramicrotexture.
3.The above results show that the content and changes of AQP-4 and MMP-9 have big relationship with cerebral edema after hemorrhage,they may lead to permeability in BBB and increasing brain tissue water.
4.The above results show that the content and changes of Caspase-3,Bcl-2.have big relationship with cerebral apoptosis after hemorrhage.
5.The symptom became better after electro-nape acupuncture therapy,
one of the mechanism of anti-edema and anti-apoptosis by acupuncture may adjust the expression of AQP-4,MMP-9,Caspase-3 and Bcl-2,diminish break in BBB,degrade brain water content,improve symptom accompanied with cerebral edema and apoptosis.
方法:本实验用健康雄性(wistar)大鼠144只,体重250-300克,按随机数字表分为A、B、C三组,每组又各分为12h、24h、3d、7d四个小组。每小组每时间点各12只动物。动物经10%水合氯醛腹腔麻醉(400mg/kg体重),头顶备皮后将动物固定于三维立体定位仪上,局部皮肤处理后以前囱为坐标原点,向大鼠尾侧0.2mm,大鼠右侧2.9mm,确定注射点坐标,用牙科钻钻孔约直径1.0mm(在右尾状核位置),A组(对照组)注入2ul0.9%的生理盐水,B组(模型组)C组(电项针组)均用微量注射器吸取含0.5u/ul胶原酶的生理盐水和7u/ul肝素的生理盐水各1.0ul注入,每组于注射完毕退出针后,缝合头皮,并于12h、24h、3d、7d参照Longa FZ五级评分法进行神经功能学评分,评分完毕后,按要求处置,测定脑含水量,及脑组织形态学观察,超微结构改变及免疫组化方法观察AQP-4,MMP-9,Caspase-3和Bcl-2蛋白的表达。
结果:
1、脑出血后大鼠出现神经功能缺损,3d达高峰,之后有所下降。电项针组与模型组比较差异显著(P＜0.05)。电项针组可以降低神经功能缺损程度。
2、脑出血大鼠模型24h后脑含水量明显增高,3d达高峰,电项针组有较明显的抗脑水肿作用,各时间点比较有统计学意义(P＜0.05)。
3、HE染色显示:脑出血后24h血肿周围可见白细胞浸润,细胞间隙和血管周围间隙增宽,3d上述病变加重,并见大量神经细胞变性坏死,7d仍有增生的胶质细胞,从病变的程度和范围看,电项针组的病理改变要轻于模型组。
4、电镜观察电项针组神经细胞超微结构的变化明显改善;与模型组比较电项针组神经元细胞内,可见高尔基,线粒体和其他细胞器结构完整,突触膜活性区,突触小泡增多。
5、AQP-4表达;模型组中3d达高峰,各时点均显著高于对照组;电项针组的表达显著低于模型组(P＜0.01)。
6、MMP-9表达;模型组3d达高峰,各时点均显著高于对照组;电项针组的表达显著低于模型组(P＜0.01)。
7、Caspase-3表达;模型组24小时达高峰,各时点均显著高于对照组;电项针组的表达显著低于模型组(P＜0.01)。
8、Bcl-2表达;模型组24小时达高峰,各时点均高于对照组;电项针组的表达显著高于模型组(P＜0.01)。
结论:
1、电项针能明显降低脑出血大鼠模型神经功能缺损评分,促进神经功能恢复。
2、通过血肿周围脑组织形态学,血脑屏障超微结构,脑组织水肿带超微结构的观察与对比,电项针刺能够有效调整微观组织结构的病理改变程度。
3、大鼠脑出血后AQP-4与MMP-9的释放与激活,是脑出血后早中期脑水肿形成的重要因素之一,导致BBB通透性增加而造成脑水含量增加。
4、大鼠脑出血后Caspase-3与Bcl-2的释放与激活,是脑出血后脑细胞凋亡相关的重要因素。
5、电项针治疗具有抗脑出血后脑水肿的作用及减轻脑细胞凋亡的作用,机制之一是对AQP-4,MMP-9,Caspase-3表达的抑制,Bcl-2表达的增加,使BBB开放程度减小,降低脑组织含水量,减轻脑水肿程度及保护神经细胞。
Objective:To research the mechanism of control factor in which electro-nape acupuncture therapy influences the brain edema and apoptosis occurred from intracerebral hemorrhage,through the experiment on the rats with intracerebral hemorrhage.
Method:healthy male wistar rats(weight:250-300g) were randomly divided into three groups:A,B and C,each group was again randomly divided into four smaller groups;12h、24h、3d、7d four time points,the rats were prepared by rules.The rats in group A were injected 0.9%physiological saline 2ul,the rats in group B and C were injected 0.9% physiological saline with 0.5u/ul collagenase 1ul and 0.9%physiological saline with 7u/ul heparin 1ul,then observe the information and data at assigned time:Neurological deficit scale,the brain tissue water content,braintissue patho-form,braintissue ultramicro-texture and AQP-4,MMP-9,Caspase-3 and Bcl-2 by immunity histochemistry method.
Results:
1.the recordings indicate there is Neurological deficit scale in hemorrhage rats,the peak occurred at 3d and descent then.There are significant disparity between model group and treating group.
2.The brain tissue water content step up after 24h and the peak occurred at 3d,there are significant disparity between model group and treating group.
3.Light-microscope shows there's severe pathological change in brain hemorrhagic model group,Nerve cells and colloidal cells swell,and in cell space there's vacuoles of different sizes and the cell space increases.In treating group,hemorrhage and cell dropsy are distinctly alleviated.
4.Electron microscope results show that the cerebral ultrastructure was significantly meliorated in treating group;There were plenty of golgicomplexes in neuron,the structure of mitochondrion and other cell organs were full and there were more synaptic vesicles in treating group.
5.The AQP-4 expression in model group reach peak at 3d,there are significant disparity between model group and treating group(P＜0.01).
6.The MMP-9 expression in model group reach peak at 3d,there are significant disparity between model group and treating group(P＜0.01)
7.The Caspase-3 expression in model group reach peak at 24h,there are significant disparity between model group and treating group(P＜0.01)
8.The Bcl-2 expression in model group reach peak at 24h,there are significant disparity between model group and treating group(P＜0.01)
Conclusion:
1.Electro-nape acupuncture therapy reduces Neurological deficit scale in hemorrhagerats,improves the nervous function.
2.Through observing and comparing braintissue morphology around hematoma,BBB ultramicro-texture,ultramicro-texture of braintissue-edema zone,Electro-nape acupuncture therapy improves pathological change of braintissue-ultramicrotexture.
3.The above results show that the content and changes of AQP-4 and MMP-9 have big relationship with cerebral edema after hemorrhage,they may lead to permeability in BBB and increasing brain tissue water.
4.The above results show that the content and changes of Caspase-3,Bcl-2.have big relationship with cerebral apoptosis after hemorrhage.
5.The symptom became better after electro-nape acupuncture therapy,
one of the mechanism of anti-edema and anti-apoptosis by acupuncture may adjust the expression of AQP-4,MMP-9,Caspase-3 and Bcl-2,diminish break in BBB,degrade brain water content,improve symptom accompanied with cerebral edema and apoptosis.
引文
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