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目的:探讨钙通道阻断剂(CCB)非洛地平对载脂蛋白E基因敲除(apoEKO)小鼠动脉粥样硬化斑块及烟酰胺腺嘌呤二核苷酸[NAD(P)H]氧化酶的影响。方法:apoEKO小鼠随机分为普通饮食组、高胆固醇饮食组、高胆固醇饮食加非洛地平组。无创血压系统测小鼠血压;内眦动脉取血检测血清TC和TG水平;冷冻切片光镜下定位主动脉根部,油红O染色评估斑块大小;实时定量PCR和Western blot方法检测主动脉中NAD(P)H氧化酶亚基p47phox和Rac-1表达。结果:高胆固醇饮食组小鼠血压没有明显变化,血脂明显升高(P<0.01),且斑块面积明显高于普食组(P<0.01);非洛地平可以明显减小斑块面积(P<0.01),同时还可以降低NAD(P)H氧化酶亚基p47phox和Rac-1表达(P<0.01)。结论:非洛地平可能通过阻断氧化应激反应抑制动脉粥样硬化发生发展。
AIM: To investigate the effects of calcium channel blocker (CCB) and felodipine on the atherosclerotic plaque and the nicotinamide adenine dinucleotide (NAD (P) H] oxidation in apolipoprotein E gene knockout mice. Effect of enzymes. Methods: ApoEKO mice were randomly divided into normal diet group, high cholesterol diet group, high cholesterol diet plus felodipine group. Blood pressure was measured by noninvasive blood pressure system. Serum levels of TC and TG were measured by intra-arteria arterial blood sampling. Aortic roots were located under the light microscopy in frozen sections and plaque size was assessed by oil red O staining. Real-time quantitative PCR and Western blot were used to detect the aortic NAD (P) H oxidase subunits p47phox and Rac-1 expression. Results: There was no significant change in blood pressure and blood lipids in the high cholesterol diet group (P <0.01), and the plaque area was significantly higher than that in the normal control group (P <0.01); felodipine could significantly reduce the plaque area P <0.01). In addition, p47phox and Rac-1 expressions of NAD (P) H oxidase subunit were also decreased (P <0.01). Conclusion: Felodipine may inhibit the development of atherosclerosis by blocking the oxidative stress.