【作者】 牛雯颖；

【导师】 肖洪彬；

【作者基本信息】 黑龙江中医药大学 ， 方剂学， 2011， 博士

【摘要】 目的：以气虚血瘀型冠心病心绞痛患者作为考察对象,从血液流变学和红细胞膜成分的变化来探讨导致气虚血瘀型冠心病心绞痛患者红细胞变形性及流动性降低的机制,进一步寻找血瘀证在红细胞膜上的发生机制,为临床合理诊治气虚血瘀型冠心病提供实验依据,并为其作用机制、作用靶点研究提供技术平台。方法：以老龄大鼠和青年大鼠为研究对象,取血制红细胞膜,测定血液粘度和红细胞膜成分变化,建立两者相关性的研究方法。将18例气虚血瘀型冠心病心绞痛患者、13例健康老人和10例健康青年人分为冠心病人组、健康老人对照组和青年对照组,测定血浆中的生化指标、全血粘度、血浆粘度、红细胞变形性、红细胞膜上的胆固醇含量、唾液酸含量、巯基含量、SOD活性、MDA含量、Na+-K+-ATP酶活力、膜蛋白组成以及激光共聚焦显微镜观察红细胞膜形态变化,以探讨其致病机制。结果：(1)与健康人比较,气虚血瘀型冠心病心绞痛患者全血粘度、血浆粘度均高于健康人(P<0.01,P<0.05),红细胞变形能力明显降低(P<0.01);血浆和红细胞膜上胆固醇含量明显升高(P<0.01,P<0.05)；而膜上唾液酸含量、巯基含量显著降低(P<0.01,P<0.01);尽管Na+-K+-ATP酶活性和SOD活性降低,丙二醛含量升高,但无统计学意义；(2)与青年人比较,气虚血瘀型冠心病心绞痛患者红细胞形态和骨架发生变化,F-actin含量降低并呈解聚状态；包括带1蛋白、带3蛋白、带4.1蛋白、带4.2蛋白、带5蛋白、原肌球调节蛋白和带6蛋白百分含量均显著降低,健康老人组带1、带3、带4.1、原肌球调节蛋白百分含量均显著高于气虚血瘀型冠心病人组的蛋白含量。结论：以老龄大鼠和青年大鼠为研究对象,从红细胞膜组分变化,建立了红细胞膜组分与血液粘度相关性所涉及部分指标的研究方法。气虚血瘀型冠心病心绞痛患者的全血粘度、血浆粘度显著升高,红细胞变形能力明显降低,其机制可能是由于红细胞表面唾液酸含量和巯基含量减少,膜胆固醇含量增多、红细胞膜骨架F-actin解聚,膜蛋白组成发生变化,从而导致抗氧化能力低下,膜流动性降低。更多还原

【Abstract】 Objectives:The coronary heart disease patients who were qi deficiency to blood stasis were observed in this article. The mechanism of the decreasement of red cell deformability and membrane fluidity of coronary heart disease patients were studied through the change of hemorheology and ingredient of erythrocyte membrane. The mechanism of blood stasis that happened in erythrocyte membrane was further looking for. And the results could be as the reference for diagnosis and treatment of coronary heart disease patients who were qi deficiency to blood stasis. The technology platform was established for studying of mechanism and target spot of action.Methods:The senile rats and young rats were observed in this article. Erythrocyte membrane was prepared. The change of blood viscosity and ingredient of erythrocyte membrane were determined. The research method for the relativity of them was established. Eighteen coronary heart disease patients who were qi deficiency to blood stasis, thirteen healthy old people and ten healthy young people were divided into coronary patient group and healthy old people control group and healthy young people control group. Many indexes such as biochemical indicator of plasma, whole blood viscosity, plasma viscosity, erythrocyte deformability and the content of cholesterol, sialic acid, hydrosulphonyl, MDA, activity of SOD, Na+-K+-ATP enzyme activity of erythrocyte membrane, constitute of membrane protein, change of form of erythrocyte membrane under laser scanning confocal fluorescence microscope were determined. The mechanism of causing blood stasis was investigated in this article.Results:(1) The whole blood viscosity and plasma viscosity of coronary patient are significantly higher than that of the healthy people (P<0.01,P<0.05); The red cell deformability index is lower than that of healthy people (P<0.01); The contents of cholesterol in erythrocyte membrane and plasma are significantly higher than that of the healthy people (P<0.01,P<0.05). The contents of sialic acid and hydrosulphonyl in erythrocyte membrane are significantly lower than that of the healthy people (P<0.01,P<0.01). SOD and Na+-K+-ATP enzyme activity of erythrocyte membrane are decreasing and the content of MDA is increasing. But there are not statistically significant. (2) Compare with the young people, there are some changes of red cell morphology and membrane skeleton in coronary heart disease patients who were qi deficiency to blood stasis. The content of F-actin is decreased and F-actin is depolymerization. The percentage composition of band 1 protein, band 3 protein, band 4.1 protein, band 4.2 protein, band 5 protein, band 6 protein and tropomodulin of coronary patients are significantly lower than that of the healthy young people. The percentage composition of band 1 protein, band 3 protein and band 4.2 protein of the healthy old people are significantly higher than that of coronary patients.Conclusions:The senile rats and young rats were as object of study. The research method for the relativity of blood viscosity and ingredient of erythrocyte membrane was established. The whole blood viscosity and plasma viscosity are increased significantly and the red cell deformability is decreased distinctly. The mechanism of decreasing antioxidant ability and membrane fluidity may has relationship with the following points:increasing the content of sialic acid and hydrosulphonyl, reducing the content of cholesterol in erythrocyte membrane, depolymerization of F-actin and the change of composition of membrane protein.更多还原