ACEI和Losartan对SHR肾局部RAS作用的比较

The Comparison the Effect of ACEIs and AT 1RA on Renal RAS

目的：了解基础状态动物模型肾局部ＲＡＳ的水平，观察其在用转换酶抑制剂（ＡＣＥＩ）和血管紧张素受体拮抗剂（ＡＴ１ＲＡ）干预治疗后的变化，探讨、比较这两种药物对肾保护作用的分子生物学机制。方法：用反转录聚合酶链反应（ＲＴ－ＰＣＲ）， 分别对自发性高血压大鼠（ＳＨＲ）肾皮质内ＡＣＥ和ＡＴ１ 受体ｍ ＲＮＡ表达进行测定，观察用ＡＣＥＩ或ＡＴ１ＲＡ干预治疗后的变化。结果：（１）与ＷＫＹ比，基础状态下ＳＨＲ肾皮质内ＡＣＥ和ＡＴ１受体ｍ ＲＮＡ表达均显著升高（两组Ｐ＜ ０．０５）；（２）与对照组相比，用ＡＣＥＩ后ＳＨＲ 肾皮质内ＡＣＥｍ ＲＮＡ 被抑制（Ｐ＜ ０．０５），但ＡＴ１ 受体ｍ ＲＮＡ无变化；（３）与对照组相比，用ＡＴ１ＲＡ后，ＳＨＲ肾皮质内ＡＣＥ和ＡＴ１ 受体ｍ ＲＮＡ均被抑制（两组Ｐ＜ ０．０５）。结论：ＡＣＥＩ和ＡＴ１ＲＡ 都对ＳＨＲ局部ＲＡＳ有作用，但作用机理和途径可能不同，ＡＴ１ 受体可能存在多方面调节机制。ＡＣＥＩ似乎仅作用于ＡＣＥ，对ＡＴ１ 受体可能没有直接作用；ＡＴ１ＲＡ在作用于ＡＴ１ 受体的同时。

Objective: To investigated the local RAS level in kidney of rats and its changes after the interventions of ACEI and AT 1RA in order to explore the molecular mechanism of the protective effects on kindey of these two drugs. Methods:Used RT-PCR to detect the ACE and AT 1 mRNA expressions in renal cortex of spontaneous hypertensive rats(SHR) and Wistar Kyoto rats(WKY) before and after applied ACEI or AT 1RA treatment. Results: (1)Compared with WKY, both ACE and AT 1 mRNA expressions in SHR were significantly higher( P <0.05);(2)ACE mRNA expression in SHR was inhibited after ACEI treatment( P <0.05), while these was no changes in AT 1 mRNA expression;(3)ACE and AT 1 mRNA expressions in SHR were both inhibited after AT 1RA treatment. Conclusion: Both ACEI and AT 1RA had local effects on RAS in SHR, but their mechanisms might be differenct. It was suggested that AT 1 receptor had multipule regulations pathways. ACEIs seems solely affect on ACE, while no direct effect on AT 1 receptor was found. However, AT 1RA might have effect on ACE through regulation of AT 1 receptor.