手术型高血压大鼠模型肾脏血管紧张素转换酶、血管紧张素转换酶2表达变化的研究

Study on the expression of ACE and ACE2 in kidney of hypertensive rat model caused by surgery

目的建立手术型高血压大鼠模型,观察肾脏血管紧张素转换酶(ACE)、ACE2mRNA及蛋白在各组中的表达变化情况,进一步探讨高血压发病的变化因素和相关治疗机制。方法 28只SD大鼠,随机分为对照组(n=7)、高血压组(n=7)、依那普利组(n=7,10mg·kg-1·d-1)及氯沙坦组(n=7,15mg·kg-1·d-1),其中除对照组外的21只大鼠通过不完全结扎肾动脉(保留0.7mm的动脉口径)制成高血压模型。使用RT-PCR的方法检测肾脏ACE及ACE2mRNA表达变化情况,使用免疫组织化学的方法检测肾脏ACE及ACE2蛋白表达变化情况。结果术后大鼠血压升高,造模成功;各组之间ACE、ACE2mRNA及蛋白表达程度不同;高血压组ACE表达强于其他各组(IOD=0.592,P<0.05),氯沙坦组ACE2表达强于其他各组(IOD=0.760,P<0.05);高血压组ACE与ACE2表达比例明显失衡(P<0.05),对照组、依那普利组及氯沙坦组ACE与ACE2表达比例较为平衡(P>0.05)。结论结扎肾动脉造模成功,ACE、ACE2表达的失衡是高血压发病的重要影响因素,调整两者表达的平衡是重要的治疗机制。

Objective Modeling hypertensive rat by surgery,observing the changes of ACE and ACE2 mRNA expression in various groups,to further discuss effect factors and mechanism of therapy of hypertension.Methods Twenty-eight Sprague-Dawley rats were used,which were randomly divided into four groups,Control group(n=7),Hypertensive group(n=7),Enalapril group(n=7,10 mg·kg-1·d-1) and Losartan group(n=7,15 mg·kg-1·d-1).Hypertensive rats were made by surgery except rats of control group.Renal artery were half-ligated through soft thread,and made caliber of the hole in the knot to 0.7 mm.Rats of Enalapril group and Losartan group were treated by Enalapril and Losartan after 3 weeks of surgery.Blood pressure of rats were measured by non-invasive arterial blood pressure technology.The expression of mRNA of renal ACE and ACE2 were measured by RT-PCR.The expression of proteins of renal ACE and ACE2 were measured by immunohistochemistry.Results Blood pressures of rats were increased after surgery.The expression of mRNA and proteins of ACE and ACE2 in various groups were different.The expression of mRNA and protein of ACE of Hypertensive group were higher than others(IOD=0.592,P<0.05).The expression of mRNA and protein of ACE2 of Losartan group were higher than others(IOD=0.760,P<0.05).The expression of ACE and ACE2 of hypertensive group was significantly unbalanced,but it was balanced in other groups.Conclusions Model of hypertensive rat was made successfully by the ligation of renal artery.The imbalance between the expression of ACE and ACE2 is one of the important roles of pathogenesis of hypertension.The balance between the expression of ACE and ACE2 is one of the important roles of the mechasim of therapy.