卡维地洛对高血压大鼠主动脉的保护作用

Protection of Carvedilol on the Aortic Tissue of Spontaneously Hypertensive Rats

目的 :研究卡维地洛对核因子 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 ,探讨其对血管保护的机制。方法 :18只雄性 12周龄SHR随机分为阳性组 ,卡维地洛组 ( 30mg/kg·d) ,美托洛尔组 ( 50mg/kg·d) ,灌喂 8周 ;另选同龄雄性WistarKyoto大鼠为阴性组 (n =6 )。用免疫组化法测各组主动脉NF κB、MCP 1的表达 ,ELISA法测血清MCP 1含量。结果 :与阴性组比较 ,阳性组主动脉组织中NF κB、MCP 1表达增加 (P<0 .0 1) ,且两者正相关 (r=0 .72 8,P <0 .0 1) ;血清MCP 1含量升高 1.6 4(P <0 .0 1)。 8周后 ,治疗组之间血压无明显差异 (P >0 .0 5) ,但卡维地洛更显著抑制NF -κB、MCP 1表达 (P <0 .0 5)。结论 :卡维地洛可能独立于降压外抑制NF κB的活化来调控MCP 1表达。

Objective:To study the expression of NF-κB and MCP-1 in the aortic tissue of spontaneously hypertensive rats(SHR) and the effects of Carvedilol on this exp ression. Method:Twelve-week-old male SHR (n=18) were randomly ass igned to positive control group(n=6),Carvedilol treated group (n=6)a nd Metoprolol treated group(n=6).In addition 6 twelve-week-old male W istar Kyoto rats were used as negative controls.Each rat in Carvedilol treated group and in Metoprolol treated group,was respectively given a daily dose o f 30 mg/kg Carvedilol or 50 mg/kg Metoprolo for 8 weeks by gavage,the rats from the other two groups were fed with a nomal diet.NF-κB and MCP-1 is examined by immunohistochemistry and serum MCP-1 concentrations were assayed by ELISA.Results:NF-κB and MCP-1 is significantly increased in the aorta of rats in positive control group compared with the negative controls(P <0.01).The upregulation of MCP-1 expression are positively correlated wit h NF-κB activation in positive controls (r=0.728,P<0.01).After 8 weeks tr eatment with Carvedilol or Metoprolol,the enhanced NF-κB and MCP-1 expressio n of the aorta and serum MCP-1 concentrations in Carvedilol treated group is m ore markly attenuated(P<0.05), The blood pressure level have no differen ce between the Carvedilol treated group and Metoprolol treated group.Conclusion:Treatment with Carvedilol, more markly decreas es the enhanced NF-κB and MCP-1 expression.This may reflect a new mechanism of C arvedilol contribute to the early prevention and cure of the vascular complicati on of hypertension, besides lowering blood pressure.