摘要
目的观察氯沙坦对高胆固醇血症兔主动脉组织单核细胞趋动蛋白1(MCP-1)基因表达水平和静脉血单核细胞表面黏附分子CD11b活性(CD11b)的影响。方法40只日本长耳白兔随机分为4组,每组10只。正常对照组喂以普通饲料;高胆固醇组喂以高胆固醇饲料;氯沙坦高、低剂量组在喂高胆固醇饲料同时,分别以氯沙坦粉剂25 mg/(kg.d)和10 mg/(kg.d)溶于温水中灌胃,1次/d。观察12周。实验结束时,主动脉组织经HE染色行病理学检查。用流式细胞技术检测CD11b。用RT-PCR方法检测主动脉组织MCP-1的基因表达。结果高胆固醇组血管内膜下斑块形成明显,而氯沙坦高、低剂量组斑块明显减少;高胆固醇组较对照组MCP-1 mRNA表达及CD11b活性显著增高(P<0.01);氯沙坦高、低剂量组MCP-1 mRNA表达及CD11b活性较高胆固醇组显著降低(P<0.05)。结论氯沙坦抑制组织MCP-1 mRNA的表达及降低CD11b活性,降低单核细胞内膜下浸润,其作用机制可能是氯沙坦从受体水平阻断肾素-血管紧张素-醛固酮系统。
AIM To investigate the effect of Losartan on the expression of MCP-1 mRNA and the activity of CDllb. METHODS Atherosclerotic rabbit models were made by feeding the rabbits with high cholesterol. Forty long ear Japan white rabbits were randomly divided into four groups： Group A were fed with common forage, Group B were fed with high cholesterol diet, while group C and D were fed with high cholesterol diet and simultaneously given Losartan of 25 mg/（ kg · d） and 10 mg/（ kg · d） , respectively. At the end of 12 weeks, flow cytometry analysis was applied to detect CDllb of blood samples from vein by FITC labeled anti-CDllb. The arteries were isolated and the samples adjacent to aortic arch were harvested for microscopy detection. The MCP-1 gene expressions in rabbit thoracic aorta were detected by RT-PCR. RESULTS The subintimal plaque of group B significantly increased, but the subintimal plaque of group C and D decreased significantly. Compared with those in group A, the mRNA expression of MCP-1 and CD1 l b values in group B significantly increased（P 〈0.01） while those in group C and group D significantly decreased when compared with those in group B （ P 〈 0.05 ）. There was no significant difference between group C and D. CONCLUSION Losartan retards atherogenesis by suppressing MCP-1 gene expression in tissues and deactivating circulational monocytes. The possible mechanism behind this may be that Losartan blocks RAS at the receptor level.
出处
《心脏杂志》
CAS
2007年第5期520-523,共4页
Chinese Heart Journal
