β_1肾上腺素能受体反义寡核苷酸对高血压大鼠主动脉的保护作用

Protection of Antisense Oligonucleotides of β_1-Adrenergic Receptor mRNA on Aorta of Rats with Spontaneously Hypertension

目的比较以阳离子脂质体载体(DOTAP/cholesterol)介导的β1肾上腺素能受体反义寡核苷酸(β1-ASODN)与卡维地洛(Carvedilol)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,探讨其对血管的保护机制。方法18只雄性12周龄SHR随机分为反义(ASODN)组(n=6,尾静脉注射β1-ASODN1.0mg/kg每2周一次,共4次);反向(INODN)组(n=6,尾静脉注射β1-INODN1.0mg/kg,每2周一次,共4次),Carvedilol组(n=6,30mg/(kg.d),灌喂8周)。用免疫组化测各组主动脉NF-κB、MCP-1的表达,ELISA法测血清MCP-1含量。结果8周后,INODN组与ASODN组和Carvedilol组比较,血压均有明显差异(P<0.01),NF-κB、MCP-1表达和血清MCP-1含量增加(P<0.01)。ASODN组与Carvedilol组之间血压无明显差异(P>0.05),主动脉组织中NF-κB、MCP-1表达和血清MCP-1含量两组之间无明显差异(P>0.05)。结论β1-ASODN具有持久的降压作用,并具有降压外对高血压大鼠主动脉的保护作用。

Objective To test the inhibitory ability of antisense oligonucleotides against rat β1-adrenergic receptor （β1-AR） mRNA （β1-ASODN） on the expression of NF-κB and MCP-1 in the aortic tissue of spontaneously hypertensive rats（SHRs）. Methods Twelve-week-old male SHRs （n = 18） were randomly assigned to β1-ASODN group （n = 6）, Carvedilol treated group （n = 6）and inverted oligonucleotides against rat β1-AR （β1-INODN） group（n = 6）. SHRs of β1- ASODN group and β1-INODN group were treated via tail vein injection of β1-ASODN （1.0mg·kg^-1·14d^-1） and β1-INODN （ 1.0mg·kg^-1·14d^-1 ） respectively for 8 weeks. Rats in Carvedilol treated group were given a daily dose of 30mg/kg Carvedilol for 8 weeks by gavage. NF-κB and MCP-1 were examined by immunohistochemistry and serum MCP-1 concentrations were assayed by ELISA. Results After 8 weeks treatment, there was no significant difference of the expression of NF-κB and MCP-1 in the aorta, serum MCP-1 concentrations and the blood pressure level between β1-ASODN group and Carvedilol treated group（P〉0. 05）. NF-κB and MCP-1 were significantly increased in the aorta of β1-INODN group compared with the treated groups（P〈0. 01）. Conclusion Besides the consistent effect of decreasing blood pressure,β1- ASODN contributes to the early prevention and cure of the vascular complication of hypertension.