Department of Pharmacology, Third-Grade Pharmacology Laboratory of State Administration of Traditional Chinese Medicine, Wannan Medical College, Anhui, Wuhu 241002, China.
Oxid Med Cell Longev. 2012;2012:856085. doi: 10.1155/2012/856085. Epub 2012 Nov 14.
We recently showed that combination therapy with losartan and pioglitazone provided synergistic effects compared with monotherapy in improving lesions of renal structure and function in Sprague-Dawley rats fed with a high-fat, high-sodium diet and 20% sucrose solution. This study was designed to explore the underlying mechanisms of additive renoprotection provided by combination therapy. Losartan, pioglitazone, and their combination were orally administered for 8 weeks. The increased level of renal malondialdehyde and expression of nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) and nitrotyrosine as well as the decreased total superoxide dismutase activity and copper, zinc-superoxide dismutase expression were tangible evidence for the presence of oxidative and nitrative stress in the kidney of model rats. Treatment with both drugs, individually and in combination, improved these abnormal changes. Combination therapy showed synergistic effects in reducing malondialdehyde level, p47(phox), and nitrotyrosine expression to almost the normal level compared with monotherapy. All these results suggest that the additive renoprotection provided by combination therapy might be attributed to a further reduction of oxidative and nitrative stress.
我们最近的研究表明，与单药治疗相比，洛沙坦联合吡格列酮治疗可协同改善高脂高盐饮食和 20%蔗糖溶液喂养的 Sprague-Dawley 大鼠的肾脏结构和功能损伤。本研究旨在探讨联合治疗提供附加肾脏保护作用的潜在机制。洛沙坦、吡格列酮及其联合用药经口给予 8 周。肾脏丙二醛水平升高，烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基 p47(phox)和硝基酪氨酸表达增加，总超氧化物歧化酶活性和铜锌超氧化物歧化酶表达降低，这些都是模型大鼠肾脏存在氧化和硝化应激的明显证据。两种药物单独和联合治疗均可改善这些异常变化。与单药治疗相比，联合治疗在降低丙二醛水平、p47(phox)和硝基酪氨酸表达方面具有协同作用，几乎可恢复至正常水平。所有这些结果表明，联合治疗提供的附加肾脏保护作用可能归因于进一步降低氧化和硝化应激。
