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阿利吉仑和缬沙坦联合治疗可改善高血压肾损伤大鼠的病情。

Aliskiren and valsartan in combination is a promising therapy for hypertensive renal injury in rats.

机构信息

a Department of Pharmacology, Faculty of Medicine , King Abdulaziz Univerisity , Gedah , Saudia Arabia.

出版信息

Clin Exp Hypertens. 2018;40(6):560-568. doi: 10.1080/10641963.2017.1407333. Epub 2017 Nov 27.

Abstract

UNLABELLED

Neither ACEI nor ARBs completely repress the RAAS. Aliskiren is a newer agent that inhibits renin. However, it increases the biosynthesis and secretion of renin and prorenin, that might induce renal tissue damage. This study was conducted to investigate the renoprotective effects of aliskiren and valsartan the ARB, either alone or in combination, on hypertensive nephropathy induced by L-NAME. Aliskiren (50 mg/kg/daily i.p.), valsartan (10 mg/kg daily i.p.) alone or in half dose combination were administered with L-NAME (30-40 mg daily in drinking water) for 8 weeks. Aliskiren and valsartan significantly reduced systolic blood pressure, proteinuria, serum creatinine, blood urea nitrogen, oxidative stress, and structural renal injury although not to the same extent. Valsartan reduced systolic blood pressure and proteinuria in L-NAME treated rats more significantly than aliskiren. However, glomerular collapse index and the expansion of interstitial tissue were significantly attenuated by aliskiren than by valsartan. Cotreatment with aliskiren and valsartan markedly reduced the oxidative stress and further reduced the glomerular collapse and the expansion of interstitial tissue compared with aliskiren monotherapy.

CONCLUSION

These results suggest that therapies aimed at different targets within the RAAS may have additional effects in attenuating structural injury in experimental hypertensive nephropathy.

摘要

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ACEI 和 ARB 均不能完全抑制肾素-血管紧张素系统。阿利克仑是一种新型的抑制肾素的药物。然而,它会增加肾素和前肾素的生物合成和分泌,这可能会导致肾组织损伤。本研究旨在探讨阿利克仑和血管紧张素受体阻滞剂(ARB)缬沙坦单独或联合应用对 L-NAME 诱导的高血压肾病的肾保护作用。阿利克仑(50mg/kg/天腹腔注射)、缬沙坦(10mg/kg/天腹腔注射)单独或半剂量联合应用于 L-NAME(每日 30-40mg 溶于饮用水中),共 8 周。阿利克仑和缬沙坦可显著降低收缩压、蛋白尿、血肌酐、血尿素氮、氧化应激和结构肾损伤,尽管程度不同。缬沙坦降低收缩压和蛋白尿的作用比阿利克仑更显著。然而,肾小球塌陷指数和间质组织扩张明显减轻,阿利克仑比缬沙坦更明显。与阿利克仑单药治疗相比,阿利克仑和缬沙坦联合治疗可显著降低氧化应激,并进一步降低肾小球塌陷和间质组织扩张。

结论

这些结果表明,针对肾素-血管紧张素系统不同靶点的治疗方法可能对减轻实验性高血压肾病的结构损伤有额外的作用。

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