【摘要】 目的　研究Gαq/ 11介导的信号转导通路在 2K1C肾性高血压大鼠心脏和主动脉中的变化以及卡托普利治疗对其的影响。方法　制备 2K1C肾性高血压大鼠模型 ,于术后 4～ 8周给予卡托普利 (15 0mg/kg) ,观察尾动脉收缩压、左室重与体重之比和主动脉形态学改变。测定心脏和主动脉中Gαq/ 11含量和磷脂酶C(PLC)活性。结果　 2K1C肾性高血压大鼠在术后 4周和 8周出现明显的高血压、心肌肥大和主动脉增厚 ,心脏和主动脉中Gαq/ 11含量明显增加。卡托普利治疗 4周可以降低血压并逆转心肌肥大 ,心脏Gαq/ 11含量及PLC活性分别降低了 15 .8%和 30 9% ,而主动脉中Gαq/ 11含量及PLC活性均无变化。结论　Gαq/ 11介导的信号转导通路参与 2K1C肾性高血压的发生和维持。卡托普利可以逆转心肌肥大 ,这一作用可能是通过抑制血管紧张素Ⅱ (AngⅡ )的生成从而消除AngⅡ导致的Gαq/ 11介导的信号转导通路的激活而实现的更多还原

【Abstract】 Objective To investigate the alteration of Gαq/11 mediated signal transduction pathway in heart and aorta of 2K1C renal hypertensive rats and the effect of captopril treatment. Methods Renal hypertension was performed by placing a sliver clip around the left renal artery. Captopril (150 mg/kg) was given from 4 to 8 weeks after operation. Systolic blood pressure was recorded by the tail cuff method each week after surgery, the ratio of left ventricular weight to body weight (LV/BW) and morphologic changes in aorta were measured at 4 and 8 weeks after operation. The levels of Gαq/11 in heart and aorta were detected by Western Blot analysis, and phospholipase C (PLC) activities were determined by using PIP 2 as substrate. Results 2K1C renal hypertensive rats had significant hypertension, cardiac hypertrophy and aorta thickening 4 and 8 weeks after operation. Systolic blood pressure and the LV/BW decreased to the level of sham group 4 weeks after captopril treatment while the morphologic change in aorta was not significant. For 2K1C group, Gαq/11 levels and PLC activities increased dramatically both in heart and in aorta at 4 weeks that remained at high levels until 8 weeks after the operation. After captopril treatment, the Gαq/11 level and PLC activity in heart decreased by 15.8% and 30 9% respectively with no changes in aorta. Conclusion Gαq/11 mediated signal transduction pathway participated in the development and maintain of 2K1C renal hypertension. Captopril reversed cardiac hypertrophy and this effect may be attributed by inhibiting the formation of angiotensin Ⅱ and, therefore, abolishing the activation of Gαq/11 mediated signal transduction pathway induced by angiotensin Ⅱ.更多还原