β3-AR阻断剂SR59230A对大鼠胸主动脉张力及microRNA表达的影响

Effect of β_3-AR antagonist SR59230A on the tension and microRNA expression of rat thoracic aorta

目的:探讨β_3肾上腺素受体(β_3-AR)阻断剂SR59230A(SR)对大鼠胸主动脉张力和micro RNA(miRNA)表达的影响。方法:44只正常雄性SD大鼠,24只用于观察SR对离体胸主动脉环张力的影响。另20只SD大鼠随机分为对照组(control)及SR组(n=10),SR组大鼠给予SR腹腔注射,control组大鼠给予等量生理盐水腹腔注射。给药5周后2组大鼠进行无创血压测量,并检测胸主动脉环对去甲肾上腺素诱导的张力;留取2组大鼠胸主动脉组织,检测SR对大鼠胸主动脉miRNA表达的影响。结果:(1)SR预孵时30 mmol/L KCl引起的离体血管环收缩张力增加(P<0.05);(2)SR在体给药5周后大鼠收缩压升高(P<0.05);(3)SR在体给药后去甲肾上腺素(NA)浓度为1μmol/L和10μmol/L时诱导大鼠胸主动脉环张力增加(P<0.05,P<0.01);(4)SR组大鼠胸主动脉18个miRNA表达下调,其中7个有统计学意义,分别是rno-miR-143-3p、rno-miR-29b-3p、rno-miR-31a-5p、rno-let-7b-5p、rnomiR-214-3p、rno-miR-222-3p和rno-miR-352;11个表达上调,其中4个有统计学意义,分别是rno-miR-206-3p、rnomiR-223-3p、rno-miR-342-3p、rno-miR-499-5p。结论:SR59230A可引起大鼠胸主动脉血管张力增加,在体给药后可使大鼠收缩压升高及胸主动脉rno-miR-143-3p、rno-miR-29b-3p、rno-miR-31a-5p、rno-let-7b-5p、rno-miR-214-3p、rnomiR-222-3p、rno-miR-352表达下调和rno-miR-206-3p、rno-miR-223-3p、rno-miR-342-3p、rno-miR-499-5p表达上调。

Objective： To explore the effects of SR59230 A on the tension and micro RNA（ miRNA） expression of rat thoracic aorta. Methods： Forty-four SD rats were used in the experiment. Twenty-four rats were used to observe the effect of SR on the tension of thoracic aortic rings. Another 20 rats were randomly divided into control（ n = 10） and SR group（ n = 10）. Rats in SR group were injected SR intraperitoneally,and in control group were given 0. 9% of saline. After 5 weeks,the blood pressure of all rats were measured. Then the tension to NA and the expression of miRNA of thoracic aorta rings were measured. Results：（ 1） The tension of thoracic aortic rings responding to 30 mmol / LKCl were increased by pretreatment of SR（ P〈0. 05）;（ 2） After 5 weeks injection of SR,systolic pressure was increased（ P〈0. 05）;（ 3） The tension in SR group was increased in presence of 1 μmol / L and 10 μmol / L of NA（ P〈0. 05,P〈0. 01）.（ 4） After 5 weeks of SR in vivo application,18 miRNA were down-regulated,7 of them had statistical significance,they were rno-miR-143-3p,rno-miR-29b-3p,rno-miR-31a-5p,rno-let-7b-5p,rno-miR-214-3p,rno-miR-222-3p and rno-miR-352; 11 miRNA were up-regulated,4 of them had statistical significance,they were rno-miR-206-3p、rno-miR-223-3p、rno-miR-342-3p and rno-miR-499-5p respectively. Conclusion： SR59230 A increased the tension of rat thoracic aorta. In vivo administration of SR led to increase of systolic pressure of rat,down-regulation of rno-miR-143-3p、rno-miR-29b-3p、rno-miR-31a-5p、rno-let-7b-5p、rno-miR-214-3p、rno-miR-222-3p、rno-miR-352 and up-regulation of rno-miR-206-3p、rno-miR-223-3p、rno-miR-342-3p and rno-miR-499-5p.