氯沙坦对糖尿病大鼠肾组织血管紧张素Ⅱ及其1型受体mRNA表达的影响

Effects of losartan on the levels of angiotensinⅡ and its type-1 receptor in diabetic rat kidney

目的研究氯沙坦对实验性糖尿病大鼠肾组织血管紧张素Ⅱ(AngⅡ)1型受体mRNA表达的影响。方法纯种雄性Wistar大鼠分为3组,A组(n=11)为正常对照组,B组(n=11)为糖尿病为干预组,C组(n=9)为糖尿病大鼠氯沙坦干预组。以链脲佐菌素制备糖尿病大鼠模型。饲养18周后取出肾脏检测AngⅡ水平、AngⅡ1型受体mRNA表达,收集24h尿测定尿白蛋白排泄及肌酐并心脏内取血检测血AngⅡ及肌酐。AngⅡ1型受体mRNA表达采用RT-PCR,以-actin作为内对照。尿白蛋白排泄采用大鼠白蛋白特异的酶免疫分析试剂盒。结果血、肾组织AngⅡ在A、B、C三组间无显著性差异。肾组织AngⅡ1型受体mRNA表达在B组大鼠(0.62±0.17)显著低于A组(1.13±0.82,P<0.01)及C组(1.13±0.62,P<0.01)。尿白蛋白排泄在B组大鼠(2.18±1.98mg/d)显著高于A组(0.41±0.47mg/d,P<0.01)及C组(0.65±0.89mg/d,P<0.01)。结论氯沙坦处理能升高糖尿病大鼠肾组织的AngⅡ1型受体mRNA表达,但不改变血液及肾组织AngⅡ水平。

Objective To investigate the effect oflosartan, an angiotensin Ⅱ type-Ⅰ receptor （ATIR） antagonist, on the levels ofangiotensin Ⅱ （Ang Ⅰ ） and ATIR in diabetic rat kidney. Methods Male Wistar rats were divided into 3 groups, group A （n=11） served as the control group, group B （n=11） included the diabetic rats （induced by intraperitoneal injection of streptozotocin） without any therapy, and group C （n=9） diabetic rats treated with losartan. After 18 weeks of treatment, the kidneys were taken from all the rats to measure the expression ofATIR mRNA by RT-PCR and detect the Ang H level. Blood was also drawn from the heart to measure Ang Ⅱ level, and 24-hour urine was collected to measure albumin level （urine albumin excretion, UAE） with rat albumin enzyme immunoassay kit. Results The blood and renal Ang Ⅱ levels showed no significant difference between the 3 groups. The expression of renal ATIR mRNA in group B （0.62±0.17） was significantly lower than that in group A （1.13±0.82, P〈0.01） and group C （1.13±0.62,P〈0.01）. UAE in group B （2.18±1.98 mg） was significantly higher than that in group A （0.41±0.47 mg/d, P〈0.01） and C （0.65 ±0.89 mg/d, P〈0.01）. Conclusion Losartan can increase the expression ofATIR mRNA in diabetic rat kidneys without altering the blood and renal Ang Ⅱ levels.