脉络“络气虚滞”动物模型的建立与评价

Study on Animal Model of "Stagnancy of Lo-qi of Ending-vessel in a Deficiency Condition"

目的:探讨络脉"络气虚滞"动物模型的建立方法,为"络气虚滞"的临床研究和中药新药研究提供理想的动物模型。方法:选用8周龄SD大鼠,采用力竭性跑台运动,并结合基础饮食(5g.100g-1体质量)建立气虚证候模型,同时采用200ng·min-1·kg-1血管紧张素Ⅱ(AngⅡ)(背部埋埴AngⅡ药物缓释泵)损伤血管,建立大鼠脉络"络气虚滞"的病理证候复合模型,补气药物组对所建模型予以验证。实验分成正常组、运动组(基础饮食)、AngⅡ组、复合模型组和药物组5组,每组10只。用放射免疫法测定血液中内皮素(endothelin-1,ET)、去甲肾上腺素(norepinephrine,NE)、AngⅡ、促肾上腺皮质激素(adreno-coticotropic hormone,ACTH)、白介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor,TNF-α)含量,扫描电镜观察主动脉内皮形态的变化。结果:运动组、AngⅡ组、复合模型组均出现内皮损伤,血液中ET、IL-6、TNF-α均有不同程度的升高,以复合模型组改变明显。符合模型组出现气虚症状,内皮细胞充血、水肿、脱落,内弹力板暴露,而ACTH、NE下调,药物组运动耐力明显改善,内皮损伤轻。结论:采用基础饮食、力竭运动及AngⅡ多因素建立络脉"络气虚滞"病理症候复合模型可行,基本符合中医气虚证候特点和现代医学血管损伤病理变化。

Objective：To establish the animal model of stagnancy of lo-qi of ending-vessel in a deficiency condition. Methods： The animal model of Qi-deficiency was induced by starvation,exhausted exercise in 8-week-old SD rat and endothelium injury was induced by angiotensinⅡosmotic mini-pump implanted subcutaneously with a released rate of 200 ng/kg per min for 14 days. 30 SD rats were divided into 5 groups：control group,fatigue group, angiotensinⅡ group, fatigue conbined angiotensinⅡgroup, rensen-apagogic group. All animals were sacrificed in 14th day. In apagogic group renshen（0.008 g·mL^-1·100 g^-1） was used by intraperitoneal injection after AngiotensinⅡpump were used. The general macroscopic and microcosmic indicators were monitored. The content of endothelin（ET）、norepinephrine（NE）, adrenocoticotropic hormone（ACTH）, interleukin-6 （IL-6） and tumor necrosis factor-α（TNF-α）in the blood were examined by radio-immunity or ELISA methods.The morphology of endothelial cell in the thoracic aorta were observed by scanning electron microscope. Results： The phenomina of endothelium injury and elevated parameters of IL-6 and TNF-α in three group incluing fatigue group, angiotensinⅡ group, fatigue conbined angiotensin Ⅱ group.The model rats were almost in accordance with the peculiarity of Qi-dificiency and endothelial dysfunction and the pathologic alterations of endothelium injury. the congestion,swelling, denudation of endothelial cell were seen in the angiotensinⅡ group, only light changes observed in fatigue group. Compared with these two group, the endothelial in fatigue conbined angiotensinⅡ group were injuried badly. The serum level of Endothelin, IL-6 and TNF-α were higher than fatigue group and angiotensinⅡ group. The renshen enhanced exercise endurance apparently and alleviated injured endothelium. Conclusion：The study suggests that this kind of nimal model of combination of disease with syndrome should be used in the study of stagnancy of lo-qi of ending-vessel in a deficiency condition.