氯沙坦抗动脉粥样硬化作用及对核因子κB mRNA影响的实验研究

目的　观察氯沙坦抗动脉粥样硬化作用及其对核因子κB基因表达水平的影响。方法　 40只日本长耳白兔随机分为 4组 ,每组 10只。A组喂以高胆固醇饲料 ;B、C组在喂高胆固醇饲料同时 ,分别以氯沙坦粉剂 10mg·kg-1·d-1和 2 5mg·kg-1·d-1溶于温水中灌胃 ,1d 1次 ;D组为正常对照组 ,喂以普通饲料。观察 12wk。实验结束时 ,分别抽静脉血测血脂。麻醉后分离血管段 ,取主动脉弓处的血管组织行组织学和电镜检查 ,剩余的血管段制成组织匀浆用放免法检测主动脉组织AngⅡ的含量。用RT PCR方法检测主动脉组织NF κB的基因表达。结果　A组动脉内膜下斑块形成明显 ,而B、C组斑块形成减少 ;A组NF κBmR NA表达增高 (P <0 0 1vsD组 ) ,B、C组NF κBmRNA表达与D组比较无差异 (P >0 0 5 ) ;B、C组之间差异无统计学意义 (P >0 0 5 )。结论　氯沙坦具有抗动脉粥样硬化的作用 ,其部分机制可能与从受体水平阻断肾素 -血管紧张素-醛固酮系统 (RAAS) ,抑制组织NF κBmRNA的表达 ,而降低单核细胞内膜下浸润有关

Experimental study of the effect of Losartan on the Antiatherogenetic mechanism and nuclear Factor-κB mRNA expression

AIM To investigate the antiatherogenetic mechanism and the effect on nuclear factor κB mRNA expression of Losartan. METHODS Atherosclerotic rabbit models were dupticated by feeding with high cholesterol. Forty long ear Japan white rabbits were randomly divided into four groups(A,B,C,D).Group A were fed with high cholesterol diet, group B and C were fed with high cholesterol diet and given losartan of 10 mg·kg -1 ·d -1 and 25 mg·kg -1 ·d -1 , group D were fed with common forage. At the end of 12 weeks, blood samples were obtained from vein for detection of serum lipid.These rabbits were killed . The vascular vessles were isolated, and the aortic archs were used for tissue review and electron microscopy dectection. The NF κB gene expressions in rabit thoracic aorta were detected by RT PCR. RESULTS The subintimal plaque of group A was significantly increased, but the subintimal plaque of group B and C was decreased significantly. Compared with group D, the mRNA expression of NF κB of the aortic tissue in group A were significantly increased( P< 0 01). But in groups B and C, no significant changes were observed( P> 0 05 vs group D). There were no siginificant difference between group B and C( P> 0 05). CONCLUSION Losartan can retard atherogenesis partly by suppression of NF κB gene expression in tissue by anti RAS at receptor level and inhibit subintimal immigraton of monocytes.