Previous studies in our laboratory have suggested that P2X7 could contribute to the progression of diabetic nephropathy and modulated klotho expression. The aim of this study was to investigate if P2X7 receptor is related to the expression of klotho in the onset of diabetic nephropathy in rats. Seven-week-old male Wistar rats weighing 210 g were all uninephrectomized; two-third of the animals were induced to diabetes with 60 mg/kg streptozotocin i.v., and one-third received its vehicle (control rats). At 4th day of the fifth week of the protocol, half of the diabetic rats received a small interfering RNA targeting for P2X7 mRNA, and the other half received its vehicle. Euthanasia was made at the eighth week. Diabetic animals reproduced all classic symptoms of the disease; besides, they showed reduced renal function and low NO bioavailability; also, SOD1, SOD2, and catalase were increased, probably due to the oxidative stress which was elevated in this situation. Metabolic data of diabetic rats did not change by silencing P2X7 receptor. For the other hand, silencing P2X7 was able to contribute to balance oxidative and nitrosative profile, ultimately improving the renal function and increasing plasma and membrane forms of klotho. These findings suggest that the management of P2X7 receptor can benefit the kidneys with diabetic nephropathy. Further studies are needed to show the therapeutic potential of this receptor inhibition to provide a better quality of life for the diabetic patient.

中文翻译：

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针对肾脏的 P2X7 siRNA 会增加 klotho 并延缓实验性糖尿病肾病的进展。

我们实验室之前的研究表明，P2X7 可能促进糖尿病肾病的进展并调节 klotho 表达。本研究的目的是探讨大鼠糖尿病肾病发病过程中 P2X7 受体是否与 klotho 的表达相关。7周龄雄性Wistar大鼠，体重210g，全部未切除肾；三分之二的动物用 60 mg/kg 的链脲佐菌素静脉注射诱发糖尿病，三分之一的动物接受其媒介物（对照大鼠）。在方案第五周的第四天，一半糖尿病大鼠接受了针对 P2X7 mRNA 的小干扰 RNA，另一半接受了其载体。安乐死是在第八周进行的。患有糖尿病的动物再现了该疾病的所有典型症状；此外，他们表现出肾功能下降和NO生物利用度低；此外，SOD1、SOD2 和过氧化氢酶也增加，这可能是由于在这种情况下氧化应激升高所致。沉默P2X7受体并没有改变糖尿病大鼠的代谢数据。另一方面，沉默 P2X7 能够有助于平衡氧化和亚硝化谱，最终改善肾功能并增加 klotho 的血浆和膜形式。这些发现表明，P2X7 受体的管理可以使糖尿病肾病患者的肾脏受益。需要进一步的研究来证明这种受体抑制的治疗潜力，为糖尿病患者提供更好的生活质量。