辛伐他汀对高血压大鼠主动脉NF-κB和MCP-1表达的影响

Effect of Simvastatin on the Expression of NF-κB and MCP-1 in Aorta of Spontaneously Hypertensive Rats

目的研究他汀类药物对核因子κB(NF -κB)、单核细胞趋化蛋白 -1(MCP -1)在自发性高血压大鼠 (SHR)大血管中表达的影响 ,探讨其预防动脉粥样硬化 (AS)的可能机制。方法20只12周龄雄性SHR随机分为SHR组和辛伐他汀 (simvastatin)组,simvastatin组用simvastatin5mg/kg·d灌胃8周 ,另取10只同龄雄性京都种Wistar大鼠为WKY组 ,免疫组化测各组主动脉NF -κB、MCP-1的表达 ,ELISA测血清MCP-1含量。结果SHR组主动脉组织中NF-κB、MCP-1表达及血清MCP-1含量显著增加 (P<0.01) ,且MCP -1表达与NF -κB活化正相关(r=0.728,P<0.01) ;simvastatin组NF -κB、MCP -1表达和血清MCP -1含量显著降低 (P<0.01)。SHR组及simvastatin组之间血压及血清总胆固醇、总甘油三脂水平无明显差异(P>0.05)。结论他汀类药物可能独立于降脂外部分通过抑制NF-κB的活化来调控MCP-1表达而抗AS。

Objective To study expression of NF-κB and MCP-1in the aortic tissue of spontaneously hypertensive rats(SHR)and the effects of statins on this expression.Methods Twelve_week_old male SHR(n=20)were randomly assigned to the positive control group(n=10)and simvastatin treated group(n=10)。In addition10twelve_week_old male Wistar Kyoto rats were used as negative controls.Rats in the treated group were given a daily dose of5mg/kg simvastatin for8weeks and the rats from other two groups were fed with normal diet.NF_κB and MCP_1were examined by immunohistochemistry and the serum MCP-1concentrations were assayed by ELISA.Results NF-κB and MCP-1were significantly increased in the aorta of rats from the positive control group comˉpared with that from the negative control group(P<0.01).Furthermore,the upregulation of MCP-1expression was positively correlated with NF-κB activation in SHR(r=0.728,P<0.01).After treatment with simvastatin for8weeks,the enhanced NF-κB and MCP-1expression in the aorta and serum MCP-1concentrations in simˉvastatin treated rats were markly attenuated compared with those in the positive control rats(P<0.05).The blood pressure and serum lipid measurements have no difference between the positive control and simvastatin treated groups(P>0.05).Conclusions Hypertension induces the upregulation of NF-κB and MCP-1in the aortic tisˉsue and an increase serum MCP-1concentrations in rats.Treatment with simvastatin markedly decreases the enˉhanced NF-κB and MCP-1expression in rats of the positive control group.This may reflect a new mechanism of statins on the anti_atherosclerosis besides lowering lipid level.