洛伐他汀对实验性家兔动脉粥样硬化形成及其相关癌基因表达作用的研究

本研究观察了洛伐他汀（ｌｏｖａｓｔａｔｉｎ，商品名：美降之）对高胆固醇饲喂的家兔动脉粥样硬化（ＡＳ）形成及其相关癌基因表达的影响。结果显示，洛伐他汀治疗组（Ｌ组）血脂水平、ＡＳ斑块面积与主动脉内膜面积的百分比、平均最大斑块厚度和平均最大斑块与中膜比值，均较动脉粥样硬化对照组（ＣＡＳ组）低（Ｐ＜０．０１）。ＣＡＳ组原癌基因Ｖ－ｓｉｓ、Ｃ－ｆｏｓ、Ｈ－ｒａｓ表达量分别是Ｌ组的２．４倍（Ｐ＜０．０１）、１．４倍、１．４倍（Ｐ＜０．０５）。提示洛伐他汀具有抗ＡＳ作用，其机制可能与降低血脂，抑制癌基因表达有关。

Effect of lovastatin on atherogenesis and expression of related oncogenes in experimental rabbits

The purposes of the study are to examine the effect of hyperlipidemia on atherogenesis and the effect of lovastatin on oncogenes related to atherosclerosis. Thirty six healthy female Japanese white rabbits were randomly separated into 3 groups. Group C (control group) fed with regular rabbit diet, group CAS fed with 1% cholesterol diet, group L fed with 1% cholesterol diet and lovastatin 10mg/day. Prior to, and at the end of 5th and 10th weeks, respectively, fasting blood samples were collected for serum total cholesterol (Tc), high density lipoprotein cholesterol (HDL C) and triglyceride (TG) assay. After sacrificing the animals, the separated entire aortas were cut longitudinally into two halves. One half was stained with oil red O and then processed for histological examination, measuring the average maximum plague (intimal ) and medial thickness with the light microscope. Planimetry was done with a computer system. The other half was homogenized and harvested total mRNA of tissues according to single step method of RNA isolation. mRNA was performed for slot blot hybridization with enzyme labeled oncogenes V sis, C fos and H ras, respectively. Hybridization signals were quantitated by densitometry using a computer system, and outcomes were calculated in relative times. The results showed that in Group L, there were 33% decreased in Tc, 30% in TG, 52% increased in HDL C, comparing to group CAS ( P <0 01). Lovastatin reduced 58% of aortic lesions comparing to group CAS ( P <0 01). Lovastatin decreased the average maximum intimal thickness, and the average maximum intimal/medial tissue ratio. Expression level of mRNA oncogenes in group CAS was enhanced more than in group L and C. It is concluded that lovastatin effectively reduced serium Tc, TG, and elevated HDL C. High expression level of oncogenes V sis, C fos, H ras were found in atherosclerotic tissue. Lovastatin inhibited expression of oncogenes related to atheroscolerosis which may be in association with hypolipidemic effects.