氟伐他汀对兔动脉粥样硬化斑块炎症的影响

Infuence of fluvastatin on plaque inflammation and Monocyte Chemoattractant Protein-1 expression in rabbit

目的观察氟伐他汀对兔动脉粥样硬化斑块炎症和单核细胞趋化蛋白-1(MCP-1)的影响。方法将24只雄性新西兰大白兔随机分为对照组、单纯高脂组和氟伐他汀组,每组8只。对照组饲予常规颗粒饲料,单纯高脂组饲予高胆固醇饲料(1%胆固醇+5%猪油),氟伐他汀组饲予高胆固醇饲料+氟伐他汀,共饲养4个月。免疫组化染色观察斑块内巨噬细胞和MCP-1的变化,并应用RT-PCR检测MCP-1基因表达情况,同时测定血清TC、TG、LDL-C水平。结果氟伐他汀组的TC、LDL-C较单纯高脂组明显降低(P均<0.01),免疫组化显示氟伐他汀组的巨噬细胞阳性面积较单纯高脂组明显减低(P<0.01),斑块内MCP-1阳性面积也明显减低(P<0.01),RT-PCR显示氟伐他汀组的MCP-1/GAPDH的mRNA表达较单纯高脂组明显减低(P<0.01)。结论氟伐他汀可以抑制单核细胞浸润,减轻血管壁的炎症反应,其中降低MCP-1的表达可能是其重要机制之一。

Objective It is to observe the influence of fluvastatin on plaque inflammation and Monocyte Chemoattractant Protein 1 （MCP- 1） expression in rabbit. Methods Twenty-four male New Zealand white rabbits were randomly and equally assigned to 3 groups： control group （ n = 8）, fed with normal diet; high-cholesterol group （ n = 8）, fed with high- cholesterol diet alone; fluvastatin group （n = 8）, fed with high-cholesterol diet and treated with fluvastatin; they were fed for 4 months. The levels of serum total cholesterol （TC）, triglyceride （TG）, low-density lipoprotein cholesterol （LDL- C） were measured. And the changes of macrophage and MCP 1 were observed by immunohistochemical staining; The MCP - 1 mRNA was analyzed by RT - PCR. Results The levels of TC and LDL- C in fluvastatin group was significantly decreased than that in high-cholesterol group （P 〈 0.01 ）. Immunohistochemical analysis showed much less stain in macrophage and MCP-1 in fluvastatin group than in high-cholesterol group （P〈0.01）. The mRNA expressions of MCP- 1 were significantly decreased in fluvastatin group than that in high-cholesterol group （P〈0.01）. Conclusion Fluvastatin can inhibit infiltration of macrophage, prevent early vascular inflammatory response of atherosclerosis and stabilize the process of atheroselerosis. Fluvastatin can reduce the expression of MCP- 1 probably is on of the acted mechanism.