目的：探讨补肾抗衰片对家兔动脉粥样硬化病变后血红素加氧酶-1（HO-1）mRNA及其相关氧化应激水平的影响。方法：将56只日本大耳白兔随机分为正常组8只，实验组48只，正常组给予普通饲料，实验组建立动脉粥样硬化模型，在第8周时，实验组随机分为模型组、补肾抗衰片组和辛伐他汀组。各组分别于给药前、给药后8、12、16周采血，最后一次采血后处死动物，无菌条件下取主动脉，用QPCR法检测主动脉HO-1 mRNA、PPARαmRNA的表达，免疫荧光技术检测HO-1蛋白水平，ELISA法检测血清HbCO、COX-2活性以及cGMP水平。结果：补肾抗衰片干预后，血清HbCO水平下降，cGMP明显升高，而COX-2活性无明显变化；HO-1免疫荧光检测发现，补肾抗衰组和辛伐他汀组绿色荧光区域均明显增加；主动脉HO-1 mRNA基因在正常组仅有少量表达，动脉粥样硬化病变组HO-1 mRNA表达增加，经补肾抗衰片干预后HO-1 mRNA表达明显升高（P<0.05），PPARαmRNA经补肾抗衰片干预后各组无均有下降的趋势。辛伐他汀也存在类似的抗氧化效应。结论：中药复方制剂补肾抗衰片在动脉粥样硬化病变中具有重要的抗氧化作用，其保护机制可能是通过调控HO-1 mRNA基因的表达及影响HO-1/CO-cGMP 通路中相关酶的活性，同时补肾抗衰片可能通过对抗过氧化反应稳定动脉粥样硬化斑块。

This study was aimed to determine effect of Bu-Shen Kang-Shuai (BSKS) Tablet on HO-1 mRNA and its associated oxidative stress levels among atherosclerotic rabbits. A total of 56 rabbits were randomly divided into the normal group (8 rabbits) and the experimental group (48 rabbits). Normal diet was given to the normal group. Atherosclerotic rabbits models were established in the experimental group. At the eighth week, rabblits in the experimental group were randomly divided into the model group, BSKS Tablet group and simvastatin group. Blood samples were collected before medication, 8-, 12-, 16-week after medication from rabbits of each group. Rabbits were sacrificed under aseptic conditions at the last blood collection. Expressions of aortic HO-1 mRNA and PPARαmRNA were measured by Q-PCR method. The level of MMP-9 was measured by immunohistochemical assay. Serum HbCO, COX-2 activity and cGMP level were measured by ELISA assay. The results showed that after the intervention of BSKS Tablet, serum HbCO level decreasd, cGMP was obviously increased. However, there was no obvious change on the COX-2 activity. The immunohistochemical assay showed that BSKS Tablet obviously reduced MMP-9 level of rabbits. There was only small amount of aortic HO-1 mRNA expression in the normal group. However, the expression of aortic HO-1 mRNA in the atherosclerosis group was increased. After intervention of BSKS Tablet, the expression of HO-1 mRNA was increased with statistical significance (P < 0.05). Simvastatin had similar antioxidant effect. It was concluded that the compound preparation of traditional Chinese medicine (TCM) BSKS Tablets had an important antioxidant effect in treatment of atherosclerosis. Its protective mechanism may be through the regulation of HO-1 mRNA gene expression and effects of HO-1/CO-cGMP pathway activities of related enzymes while peroxidation stability of atherosclerotic plaque.

国家自然科学基金委青年项目（30901905）：补肾抗衰片动态调控HO-1/CO与NOS/NO系统平衡稳定动脉粥样硬化斑块的实验研究，负责人：张光银。