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

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。

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

OBJECTIVE: To investigate the effect of losartan, an angiotensin II type-1 receptor (AT1R) antagonist, on the levels of angiotensin II (Ang II) and AT1R 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 of AT1R mRNA by RT-PCR and detect the Ang II 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 AT1R 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 of AT1R mRNA in diabetic rat kidneys without altering the blood and renal Ang II levels.