厄贝沙坦对5/6肾切除及腹主动脉缩窄大鼠左心室肥厚及心肌尿素转运蛋白B表达的影响

Effects of irbesartan on left ventricular hypertrophy and expression of urea transporter B in myocardium of 5/6 nephrectomized rats with constricted abdominal aorta

目的观察血管紧张素Ⅱ受体拮抗剂厄贝沙坦对5/6肾切除及腹主动脉缩窄大鼠左心室肥厚及心肌尿素转运蛋白B(UT-B)表达的影响。方法 SD大鼠随机分为假手术组、5/6肾切除组(肾衰组)、腹主动脉缩窄组(心衰组)、肾衰+心衰组及相应的厄贝沙坦干预组,每组8只。分组处理后,测定各组大鼠血清肌酐(SCr)、血尿素氮(BUN)、血管紧张素Ⅱ(AngⅡ)、B型利钠肽(BNP);取大鼠心脏,测定左心室质量与全心质量的比值(LVW/HW)、全心质量与体质量的比值(HW/BW)、左心室质量与体质量的比值(LVW/BW);RT-PCR和Western blotting检测心肌UT-B表达。结果与假手术组比较,肾衰组、心衰组及肾衰+心衰组大鼠出现心肌肥厚,LVW/HW、HW/BW、LVW/BW增大,血清AngⅡ和BNP水平增高,心肌组织UT-B mRNA和UT-B蛋白表达上调;肾衰组和肾衰+心衰组SCr、BUN水平升高。与肾衰组、心衰组及肾衰+心衰组比较,相应的厄贝沙坦干预组大鼠的心肌肥厚明显减轻,LVW/HW、HW/BW、LVW/BW降低,血清AngⅡ和BNP下降,心肌UT-B mRNA和UT-B蛋白表达下调。与肾衰组和肾衰+心衰组比较,相应的厄贝沙坦干预组大鼠SCr、BUN水平降低。结论 5/6肾切除及腹主动脉缩窄均可引起大鼠心功能明显下降,出现左心室肥厚,同时心肌UT-B表达增加;厄贝沙坦在改善心、肾功能的同时抑制心肌UT-B表达,UT-B可能在肾功能不全合并心力衰竭的发生中具有重要作用。

Objective To observe the effects of angiotensin Ⅱ receptor antagonist irbesartan on left ventricular hypertrophy and the expression of urea transporter B（UT-B） in myocardium of 5/6 nephrectomized rats with constricted abdominal aorta.Methods SD rats were randomly divided into the sham group,5/6 nephrectomy group,abdominal aorta constriction group,5/6 nephrectomy and abdominal aorta constriction group,and irbesartan group.Each group consisted of eight rats.Serum Cr,BUN,Ang Ⅱ,and BNP were detected after rats were sacrificed.Rat hearts were harvested and the left ventricular weight/heart weight（LVW /HW）,heart weight/body weight（HW/BW）,and left ventricular weight/body weight（LVW/BW） were measured.The expression of UT-B in myocardium was determined by RT-PCR and Western blotting.Results Compared with the sham group,rats of 5/6 nephrectomy group,abdominal aorta constriction group,and 5/6 nephrectomy and abdominal aorta constriction group had the left ventricular hypertrophy and elevated LVW /HW,HW /BW,LVW /BW,serum Ang Ⅱ,BNP,and mRNA and protein expressions of UT-B in myocardium.Levels of SCr and BUN of the 5/6 nephrectomy group and 5/6 nephrectomy and abdominal aorta constriction group increased.Compared with above three groups,rats of the irbesartan group had alleviated left ventricular hypertrophy and lower LVW/HW,HW/BW,LVW/BW,serum Ang Ⅱ,BNP,and mRNA and protein expressions of UT-B in myocardium.Compared with the 5/6 nephrectomy group and 5/6 nephrectomy and abdominal aorta constriction group,levels of SCr and BUN of the irbesartan group were lower.Conclusion5/6 nephrectomy and abdominal aorta constriction can cause significant decrease of heart function of rats,left ventricular hypertrophy,and elevated expression of UT-B.Irbesartan can improve heart and kidney functions and inhibit the expression of UT-B,which may play an important role in heart failure of rats with renal inadequacy.