| 摘要: |
| 目的探讨烟酸联合氯沙坦对兔动脉粥样硬化斑块胆固醇逆转运相关基因ATP结合盒转运体A1（ABCAl）、B族I型清道夫受体（SR-BI）和细胞外基质重建相关基因MMP-1、MMP-9mRNA表达的影响。方法50只兔分为正常对照组、动脉粥样硬化模型组（模型组）、烟酸组、氯沙坦组和烟酸＋氯沙坦组（联合治疗组），每组10只。采取高脂饮食＋球囊损伤内膜的方法建立动脉粥样硬化模型，正常对照组喂以正常饲料，其余各组喂以高脂饲料，第9周起烟酸组、氯沙坦组和联合治疗组分别在高脂饲料中添加烟酸、氯沙坦、烟酸＋氯沙坦喂养，8周后检测血脂水平，HE染色测量内膜中层厚度（IMT），实时荧光定量PCR检测ABCAl、SR-BI、MMP-1和MMP-9的mRNA表达。结果8周后与正常对照组比较，各高脂饲料喂养组TC、TG和LDL-C升高（均P＜0.01）。16周后与模型组比较，联合治疗组TC、TG和LDL-C降低，HDL-C升高，ABCAl和SR-BImRNA表达增加，而MMP-1mRNA表达降低（均P＜0.01）；主动脉IMT降低，MMP-9mRNA表达也降低（均P＜0.05）。烟酸组HDL-C、ABCAl和SR-BImRNA表达高于模型组，氯沙坦组MMP-9mRNA表达低于模型组（均P＜0.05）。结论烟酸联合氯沙坦可明显改善血脂谱及稳定动脉粥样硬化斑块，上调ABCAl和SR-BI、降低MMP-1和MMP-9mRNA的表达水平。 |
| 关键词: 烟酸类 氯沙坦 动脉粥样硬化 清道夫受体，B 类 ATP 结合盒转运子 基质金属蛋白酶 |
| DOI： |
| 分类号: |
| 基金项目: |
|
| Effects of niacin plus losartan on mRNA expressions of ABCAl , SR-BI, MMP-1 and MMP-9 in atherosclerotic plaques of rabbits with atherosclerosis |
|
JI Ningning,ZHU Yanhong
|
|
Yiwu Central Hospital
|
| Abstract: |
| Objective To investigate the effects of niacin plus losartan on mRNA expressions of ABCAl, SR-BI, MMP-1
and MMP-9 in atherosclerotic plaques of rabbits with atherosclerosis. Methods Fifty rabbits were randomly divided into normal control group(CON group), atherosclerosis model group(AS group), niacin treatment group (NIA group), losartan treatment group (LOS group) and niacin plus losartan treatment group (N＋L group) with 10 rabbits in each group. Rabbits in AS, NIA, LOS and N＋L groups underwent balloon-induced arterial wall injury and then fed with high fat diet for 8 weeks; and rabbits in CON group
were ona regular diet only. After 8 weeks the NIA group was given niacin 200 mg•kg-1•d-1, LOS group was given losartan 20 mg• kg-1•d-1, N＋L group was given niacin 200 mg•kg-1•d-1 and losartan 20 mg•kg-1•d-1. The blood lipid levels were measured after 8 weeks．The animals were sacrificed by the end of 16 weeks and pathological examination was performed．The thickness ratio of the intima to media (IMT) was measured by HE staining. The mRNA expressions of ABCAl, SR-BI, MMP-1 and MMP-9 in atherosclerotic plaques were detected by RT-PCR. Results The serum TC, TG and LDL-C levels, the aortic IMT were significantly higher in AS group than those in CON group. The mRNA expressions of ABCAl and SR-BI were significantly lower while the mRNA expressions of MMP-1 and MMP-9 were significantly higher in AS group than those in CON group (all P＜0.01). The serum HDL-C 1evel and the mRNA expressions of ABCAl and SR-BI were significantly higher in NIA group than those in AS group (all P ＜0.05)．The serum TC, TG and LDL-C levels were significantly lower while the serum HDL-C 1evels were significantly higher, the mRNA expressions of ABCAl and SR-BI were significantly higher while the mRNA expressions of MMP-1 and MMP-9 were significantly lower, and the aortic IMT was significantly lower in N+L group than those in AS group (all P＜0.05).
Conclusion Niacin plus losartan can significantly improve the lipid profile and stabilize the atherosclerotic plaques, up-regulate the mRNA expressions of ABCAl and SR-BI, and down-regulate the mRNA expressions of MMP-1 and MMP-9 in rabbits with arthrosclerosis. |
| Key words: Nicotinoc acids Losartan Atherosclerosis Scavenger receptor, Class B ATP-binding cassette trans-
porters Matrix metalloproteinases |
