摘要
目的 探讨辛伐他汀对体外培养兔血管平滑肌细胞 (VSMC)增殖的影响及机制。方法 16只雄性新西兰兔随机分为空白血清对照组和 3个不同剂量的辛伐他汀组 (5mg/kg、10mg/kg、15mg/kg) ,7d后采血并混合每组 4只兔血 ,无菌分离制备分组辛伐他汀含药血清。另采用内皮素 1刺激原代培养正常喂饲兔主动脉VSMC建立增殖模型 ,采用MTT及3 H TdR法检测分组辛伐他汀含药血清对VSMC增殖的作用 ,采用免疫细胞化学方法检测VSMCc myc、c fos抗原表达、RT PCR半定量检测c myc及c fosmRNA表达。结果 与对照组相比 ,不同分组辛伐他汀含药血清呈剂量依赖性抑制血管平滑肌细胞增殖 (P <0 0 5～ 0 0 1) ;免疫细胞化学及RT PCR结果表明 ,不同分组辛伐他汀含药血清呈剂量依赖方式抑制VSMCc fos和c mycmRNA表达(P <0 .0 5～ 0 .0 1)。结论 兔口服辛伐他汀后的血清抑制VSMC增殖 ,而辛伐他汀含药血清抑制c fos和c myc表达可能是其抑制VSMC增殖和抗动脉粥样硬化的机制之一。
Objective Using cultureed rabbit aortic vascular smooth muscle cells(VSMCs) in culture,we examine the direct antiproliferative effects of serum from simvastatin treated rabbits on VSMCs proliferation and expressions of c-fos and c-myc,Methods 16 male New Zealand white rabbits were classified randomly into four groups(n=4). Rabbits fed regular chow alone served as sreum control group,the rest gorups were fed chow plus different dosage of simvastatin(5mg/kg,10mg/kg,15mg/kg)respectively for 7 days.Cultured aortic VSMCs come from another normal rabbit fed regular chow alone.Under the condition of no toxic effects,the proliferative response was determined by -thymidine and MTT test.Proto-oncogenes c-fos and c-myc expressions were explored with immunocytochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR).Results Fotal calf serum or serum from untreated rabbits plus ET-1 stimulated -thymidine incorporation and enhanced MTT test values of VSMCs compared with that in fotal calf serum-stimulated alone.Meanwhile,serums from simvastatin treated rabbits respectively inhibited VSMC proliferation and expressed of c-fos,c-myc mRNA induced by ET-1 in a concentration-dependent manner.Conclusions Simvastatin could exerted an influence on VSMCs proliferation by mouth and its antiproliferative effect may be mediated through inhibition of c-fos and c-myc expression.
出处
《中国血液流变学杂志》
CAS
2004年第3期295-298,共4页
Chinese Journal of Hemorheology
