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咪达普利治疗对高血压大鼠肾脏水通道蛋白-2表达及尿排泄的影响。

Effects of imidapril treatment on aquaporin-2 expression in the kidneys and excretion in the urine of hypertensive rats.

作者信息

Zhao Wei, Xu Ai-Guo, Wu Jing, Guo Jing, Xu Qin-Fu, Li Dan-Dan, Zhao Yu-Miao

机构信息

Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

出版信息

Exp Ther Med. 2013 May;5(5):1327-1331. doi: 10.3892/etm.2013.1014. Epub 2013 Mar 15.

Abstract

Renal aquaporin-2 (AQP2) is critical for maintaining water balance and is associated with hypertension. Anti-hypertensive drugs, including imidapril, improve kidney function; however, it remains unclear whether these effects are mediated through the regulation of AQP2. In this study, the effects of imidapril on AQP2 expression in the kidneys and excretion in urine were assessed in hypertensive rats. Hypertension was induced in 24 rats, which were randomized into a control group, treated with water only, and an imidapril treatment group (n=12 per group). Blood and urine samples were collected from all rats to determine blood pressure (BP), serum Na, urine volume and urine osmolality after 8 weeks of treatment. Molecular and immunological techniques were used to measure the expression of AQP2 in the kidneys. Urine AQP2 concentration was detected by indirect enzyme-linked immunosorbent assay (ELISA). The concentration of plasma arginine vasopressin (AVP), a regulator of AQP2 was detected by radioimmunoassay (RIA). Hypertensive rats treated with imidapril exhibited reduced BP and 24-h urine osmolality, with a concomitant increase in 24-h urine volume, compared with control hypertensive rats (P<0.05). Additionally, the expression of mRNA, detected by RT-PCR, and AQP2 protein, detected by immunohistochemistry and western blotting, in renal tissue significantly decreased (P<0.05). Finally, urine AQP2 concentration increased while plasma AVP concentration decreased following imidapril treatment (P<0.05). These findings indicate that imidapril reduces the expression level of AQP2 in renal tissue and accelerates its excretion.

摘要

肾水通道蛋白-2(AQP2)对维持水平衡至关重要,且与高血压相关。包括咪达普利在内的抗高血压药物可改善肾功能;然而,这些作用是否通过对AQP2的调节介导尚不清楚。在本研究中,评估了咪达普利对高血压大鼠肾脏中AQP2表达及尿排泄的影响。对24只大鼠进行高血压诱导,将其随机分为仅给予水的对照组和咪达普利治疗组(每组n = 12)。治疗8周后,从所有大鼠采集血液和尿液样本以测定血压(BP)、血清钠、尿量和尿渗透压。采用分子和免疫技术测量肾脏中AQP2的表达。通过间接酶联免疫吸附测定(ELISA)检测尿AQP2浓度。通过放射免疫测定(RIA)检测作为AQP2调节剂的血浆精氨酸加压素(AVP)浓度。与对照高血压大鼠相比,接受咪达普利治疗的高血压大鼠血压降低,24小时尿渗透压降低,同时24小时尿量增加(P<0.05)。此外,通过RT-PCR检测的mRNA表达以及通过免疫组织化学和蛋白质印迹检测的肾组织中AQP2蛋白均显著降低(P<0.05)。最后,咪达普利治疗后尿AQP2浓度升高而血浆AVP浓度降低(P<0.05)。这些发现表明,咪达普利可降低肾组织中AQP2的表达水平并加速其排泄。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bd3/3671784/4ecd1793b18b/ETM-05-05-1327-g00.jpg

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