耳缘静脉注射高分子右旋糖酐致兔主As早期病变及银杏叶预防作用
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摘要
目的：通过兔耳缘静脉连续小剂量注射高分子右旋糖酐的方法,创立动脉粥样硬化早期病变I型病灶的动物模型。通过对血常规、血粘度等检测指标的分析,以及对兔胸、腹主动脉的动态病理观察,以期找到动脉外膜滋养血管微循环障碍与动脉粥样硬化早期病变的关系。从预防动脉粥样硬化早期病变的角度观察银杏叶的疗效。
方法：将36只雄性日本大耳白兔随机分为6组,每组6只,分别是生理盐水组、7天模型组、14天模型组、28天模型组、银杏叶组和羟苯磺酸钙组。均常规饲养。三个模型组分别在造模7天、14天、28天后处死,生理盐水组和两个治疗组在给药28天后处死。处死前,各组均采血行血常规、血生化、血粘度检测,将检测结果进行统计学分析。处死后,各组取胸主动脉、腹主动脉行HE染色、RAMll免疫组化染色,进行动态病理观察。
结果：血液检测指标的统计学分析结果显示,各模型组不同程度的造成了血液高聚、高粘状态,PLT、PDW、全血高切粘度、全血中切粘度、全血低切粘度、血浆粘度均高于生理盐水组(P<0.05或P<0.01)；银杏叶对血液高聚、高粘状态有一定改善作用,在PLT、 PDW、全血高切粘度、全血中切粘度、全血低切粘度、血浆粘度水平上,与7天、28天模型组比较有不同程度的降低(P<0.05或P<0.01)。动态观察各组胸主动脉、腹主动脉病理结果,在各模型组动脉内膜发现RAMll标记的阳性表达的巨噬细胞,以28天模型组为著,证实连续静脉注射小剂量高分子右旋糖酐的方法成功制备兔主动脉粥样硬化早期病变I型病灶模型。在7天、14天模型组和两个治疗组中发现动脉外膜滋养血管腔内瘀血,并在模型组中观察到动脉内膜不均匀增厚、内皮下层细胞聚集、平滑肌细胞核增多、外膜增生等动脉粥样硬化早期病变,甚至可见中膜病理性新生滋养血管的形成,而治疗组的病变较模型组轻,提示动脉外膜滋养血管循环障碍可能是动脉粥样硬化早期病变的始动因素,而动脉中膜病理性滋养血管的新生可能是局部缺血缺氧的一种代偿机制,银杏叶具有一定的抗动脉粥样硬化早期病变的作用。
结论：1通过兔耳缘静脉连续小剂量注射高分子右旋糖酐的方法能够成功创立动脉粥样硬化早期病变I型病灶的动物模型；2动脉外膜滋养血管循环障碍可能是动脉粥样硬化早期病变的始动因素之一；3银杏叶对动脉粥样硬化早期病变有一定的预防和治疗作用。
Objective:By continuously inject ing small doses of the polymer dex traan into rabbit ear marginal vein, create the animal models of type1lesions in atherosclerosis early lesions. Through analying the results of blood routine, blood viscosity and any other indexes, and dynamically observating the pahthological variation of the rabbits'thoracic and abdominal aorta, to find the relationship between microcirculatorydisturbance of advent it ia vasa vasorum and atherosclerosis early lesions. Moreover, to obervate the efficacy of Ginkgo biloba in the prevention of atherosclerosis early lesions.
Methods:Thirty-six male Japanese big ears white rabbits were divided randomly into six groups (n=6). That was normale sal ine group, seven days model group, fourteen days model group, twenty-eight days model group, Ginkgo biloba group and Calcium Dobesilate group. All the rabbits were fed general rabbit pellets. Three model groups were killed after seven days,fourteen days and twenty-eight "days respect ively. The other groups were killed after twenty-eight days. Before being killed, all the rabbits were tested blood routine, serum biochemical index, blood viscosity. The tests results were statistically analyzed. After being killed,each rabbits'thoracic and abdominal aortas were proceeded hematoxylin-eosin staining, RAM11immunohistochemical staining for the dynamic pathological observation.
Results:The statistical analysis results of the blood indexs indicated that there model groups caused different levels blood state of hypercoagulability and high viscosity. The there model groups levels of PLT, PDW, whole blood high shear viscosity, whole blood medium shear viscosity, whole blood low shearing viscosity, plasma viscosity were higher than the normal saline group (P<0.05or P<0.01). Ginkgo biloba, from a certain extent, improved the blood state of hypercoagulability and high viscosity. It's levels of PLT, PDW, whole blood high shear viscosity, whole blood medium shear viscosity, whole blood low shearing viscosity, plasma viscosity were lower than seven days model groups and twenty-eight days model group(P<0.05or P<0.01). The dynamic pathological observation findings show that the macrophages labeled by RAM11positively expressed at the intima of thoracic and abdominal aortas in thress model groups.That expression in twenty-eight model group was more notable than other tow model groups. The findings confirmed that the method of continuous intravenous injection of small doses of polymer dextran successfully built rabbit aortic type I lesions in atherosclerosis early lesions. Adventitial vasa vasorum blood stasis was found in the seven days model group, fourteen days model group and tow treatment groups. Inaddtion, the atherosclerosis early lesions such as uneven thickening of the arterial intima, subendothelial layer cell aggregation, smooth muscle cells nucleus increased and the thickening of arterial adventitia,even the generation of pathological vasa vasorum in the arterial media were found in the model groups. Compared with model groups, the lesions as mentioned were less expressed in tow treatment groups. The findings prompt that microcirculatorydisturbance of vasa vasorum may be the intial reason of atherosclerosis early lesions, the generation of pathological vasa vasorum at arterial media may be a compensatory mechanism of ischemia and anoxia, Ginkgo biloba has certain efficacy of anti-atherosclerotic early lesions.
Conclusion:1The method of cont inuously injecting small doses of the polymer dextran into rabbit ear marginal vein can successfully create the animal models of type I lesions in atherosclerosis early lesions.2The microcirculatorydisturbance of arterial adventitial vasa vasorum may be one of the intial reason of atherosclerosis early lesions.3Ginkgo biloba has certain efficacy of prevention and treatment of atherosclerosis early lesions.
方法：将36只雄性日本大耳白兔随机分为6组,每组6只,分别是生理盐水组、7天模型组、14天模型组、28天模型组、银杏叶组和羟苯磺酸钙组。均常规饲养。三个模型组分别在造模7天、14天、28天后处死,生理盐水组和两个治疗组在给药28天后处死。处死前,各组均采血行血常规、血生化、血粘度检测,将检测结果进行统计学分析。处死后,各组取胸主动脉、腹主动脉行HE染色、RAMll免疫组化染色,进行动态病理观察。
结果：血液检测指标的统计学分析结果显示,各模型组不同程度的造成了血液高聚、高粘状态,PLT、PDW、全血高切粘度、全血中切粘度、全血低切粘度、血浆粘度均高于生理盐水组(P<0.05或P<0.01)；银杏叶对血液高聚、高粘状态有一定改善作用,在PLT、 PDW、全血高切粘度、全血中切粘度、全血低切粘度、血浆粘度水平上,与7天、28天模型组比较有不同程度的降低(P<0.05或P<0.01)。动态观察各组胸主动脉、腹主动脉病理结果,在各模型组动脉内膜发现RAMll标记的阳性表达的巨噬细胞,以28天模型组为著,证实连续静脉注射小剂量高分子右旋糖酐的方法成功制备兔主动脉粥样硬化早期病变I型病灶模型。在7天、14天模型组和两个治疗组中发现动脉外膜滋养血管腔内瘀血,并在模型组中观察到动脉内膜不均匀增厚、内皮下层细胞聚集、平滑肌细胞核增多、外膜增生等动脉粥样硬化早期病变,甚至可见中膜病理性新生滋养血管的形成,而治疗组的病变较模型组轻,提示动脉外膜滋养血管循环障碍可能是动脉粥样硬化早期病变的始动因素,而动脉中膜病理性滋养血管的新生可能是局部缺血缺氧的一种代偿机制,银杏叶具有一定的抗动脉粥样硬化早期病变的作用。
结论：1通过兔耳缘静脉连续小剂量注射高分子右旋糖酐的方法能够成功创立动脉粥样硬化早期病变I型病灶的动物模型；2动脉外膜滋养血管循环障碍可能是动脉粥样硬化早期病变的始动因素之一；3银杏叶对动脉粥样硬化早期病变有一定的预防和治疗作用。
Objective:By continuously inject ing small doses of the polymer dex traan into rabbit ear marginal vein, create the animal models of type1lesions in atherosclerosis early lesions. Through analying the results of blood routine, blood viscosity and any other indexes, and dynamically observating the pahthological variation of the rabbits'thoracic and abdominal aorta, to find the relationship between microcirculatorydisturbance of advent it ia vasa vasorum and atherosclerosis early lesions. Moreover, to obervate the efficacy of Ginkgo biloba in the prevention of atherosclerosis early lesions.
Methods:Thirty-six male Japanese big ears white rabbits were divided randomly into six groups (n=6). That was normale sal ine group, seven days model group, fourteen days model group, twenty-eight days model group, Ginkgo biloba group and Calcium Dobesilate group. All the rabbits were fed general rabbit pellets. Three model groups were killed after seven days,fourteen days and twenty-eight "days respect ively. The other groups were killed after twenty-eight days. Before being killed, all the rabbits were tested blood routine, serum biochemical index, blood viscosity. The tests results were statistically analyzed. After being killed,each rabbits'thoracic and abdominal aortas were proceeded hematoxylin-eosin staining, RAM11immunohistochemical staining for the dynamic pathological observation.
Results:The statistical analysis results of the blood indexs indicated that there model groups caused different levels blood state of hypercoagulability and high viscosity. The there model groups levels of PLT, PDW, whole blood high shear viscosity, whole blood medium shear viscosity, whole blood low shearing viscosity, plasma viscosity were higher than the normal saline group (P<0.05or P<0.01). Ginkgo biloba, from a certain extent, improved the blood state of hypercoagulability and high viscosity. It's levels of PLT, PDW, whole blood high shear viscosity, whole blood medium shear viscosity, whole blood low shearing viscosity, plasma viscosity were lower than seven days model groups and twenty-eight days model group(P<0.05or P<0.01). The dynamic pathological observation findings show that the macrophages labeled by RAM11positively expressed at the intima of thoracic and abdominal aortas in thress model groups.That expression in twenty-eight model group was more notable than other tow model groups. The findings confirmed that the method of continuous intravenous injection of small doses of polymer dextran successfully built rabbit aortic type I lesions in atherosclerosis early lesions. Adventitial vasa vasorum blood stasis was found in the seven days model group, fourteen days model group and tow treatment groups. Inaddtion, the atherosclerosis early lesions such as uneven thickening of the arterial intima, subendothelial layer cell aggregation, smooth muscle cells nucleus increased and the thickening of arterial adventitia,even the generation of pathological vasa vasorum in the arterial media were found in the model groups. Compared with model groups, the lesions as mentioned were less expressed in tow treatment groups. The findings prompt that microcirculatorydisturbance of vasa vasorum may be the intial reason of atherosclerosis early lesions, the generation of pathological vasa vasorum at arterial media may be a compensatory mechanism of ischemia and anoxia, Ginkgo biloba has certain efficacy of anti-atherosclerotic early lesions.
Conclusion:1The method of cont inuously injecting small doses of the polymer dextran into rabbit ear marginal vein can successfully create the animal models of type I lesions in atherosclerosis early lesions.2The microcirculatorydisturbance of arterial adventitial vasa vasorum may be one of the intial reason of atherosclerosis early lesions.3Ginkgo biloba has certain efficacy of prevention and treatment of atherosclerosis early lesions.
引文
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