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外源性硫化氢(H2S)可降低血压并防止自发性高血压大鼠糖尿病肾病的进展。

Exogenous hydrogen sulfide (H2S) reduces blood pressure and prevents the progression of diabetic nephropathy in spontaneously hypertensive rats.

机构信息

Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.

出版信息

Ren Fail. 2012;34(2):203-10. doi: 10.3109/0886022X.2011.643365. Epub 2012 Jan 9.

Abstract

The coexistence of hypertension and diabetes results in the rapid development of nephropathy. Hydrogen sulfide (H2S) is claimed to control the vascular and renal functions. This study tested the hypothesis that exogenous H2S lowers the blood pressure and decreases the progression of nephropathy in spontaneously hypertensive rats (SHR) that were diabetic. Eighteen SHR were divided into three groups: SHR, SHR diabetic, and SHR diabetic treated with a group of Wistar-Kyoto rats serving as normotensive nondiabetic control. Diabetes was induced with streptozotocin (STZ) in two groups and one diabetic group received sodium hydrosulfide (NaHS), a H2S donor for 5 weeks. Blood pressure was measured in conscious and anesthetized states and renal cortical blood perfusion in acute studies. Plasma and urinary H2S levels, creatinine concentrations, and electrolytes were measured on three different occasions throughout the 35-day period. Diabetic SHR had higher blood pressure, lower plasma and urinary H2S levels, and renal dysfunction as evidenced by increased plasma creatinine, creatinine clearance, and decreased urinary sodium-to-potassium ratio and renal cortical blood perfusion. NaHS reduced blood pressure, increased H2S levels in plasma and urinary excretion, and reversed the STZ-induced renal dysfunction. The findings of this study suggest that the administration of exogenous H2S lowers the blood pressure and confers protection against the progression of STZ-induced nephropathy in SHR.

摘要

高血压和糖尿病并存会导致肾病迅速发展。据称,硫化氢 (H2S) 可控制血管和肾脏功能。本研究检验了以下假设:外源性 H2S 可降低血压并减缓自发性高血压大鼠 (SHR) 糖尿病肾病的进展。将 18 只 SHR 分为三组:SHR、SHR 糖尿病组和 SHR 糖尿病组,其中一组 Wistar-Kyoto 大鼠作为正常血压非糖尿病对照组。两组均用链脲佐菌素 (STZ) 诱导糖尿病,其中一个糖尿病组给予 H2S 供体硫氢化钠 (NaHS) 治疗 5 周。在清醒和麻醉状态下测量血压,并在急性研究中测量肾皮质血流灌注。在 35 天的过程中,分三次测量血浆和尿 H2S 水平、肌酐浓度和电解质。糖尿病 SHR 的血压较高,血浆和尿 H2S 水平较低,肾功能受损,表现为血浆肌酐升高、肌酐清除率降低以及尿钠钾比和肾皮质血流灌注降低。NaHS 降低了血压,增加了血浆和尿中的 H2S 排泄,并逆转了 STZ 引起的肾功能障碍。本研究结果表明,外源性 H2S 的给药可降低血压并防止 SHR 中 STZ 诱导的肾病进展。

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