The mechanism and treatment of abnormalities about Renal Hemodynamic in the early stage diabetic.

早期糖尿病肾血流动力学异常的机制及治疗.

• 批准号: 17590814
• 负责人: HASHIMOTO Seiji
• 金额: $ 2.3万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590814/
• 关键词: diabetic; ATl receptor antagonist; type 2 diabetic rats (OLETF); renal hemodynamic; アンギオテンシンレセプター; OLETラット; アンギオテンシンレセプ

The mechanisms protecting against or promoting the development of diabetic nephropathy are still not well understood. Studies were performed in type 2 diabetic rats to investigate existence and time point of onset of renal hemodynamic abnormalities. In 12 week old type 2 diabetic rats (OLETF), considered to be prediabetic, and control rats (LETO) we determined the effect of the AT1 receptor antagonist olmesartan (OLM; 5mg/kg) on total (RBF), superficial (SBF), and deep renal cortical blood flow (DBF). SBF was significantly increased by OLM in LETO, but not in OLETF. In contrast, OLM had no effect on DBF in LETO, but increased DBF in OLETF. Micropuncture studies showed that tubuloglomerular feedback (TGF) responses were reduced in OLETF (7.3 v.s 25.7%). In OLETF at about 40 weeks of age and LETO of comparable age we assessed the effect of comparable reductions of renal perfusion pressure (RPP) induced by clamping the abdominal aorta on RBF, SBF and DBF. Whereas SBF showed no significant change in both OLETF and LETO rats, DBF decreased significantly more in OLETF than LETO. TGF responses were reduced in OLETF (4.4 v.s. 18.8%). Renal corticotomy was performed to measure glomerular capillary pressure (P_<gc>). P_<gc> in OLETF was significantly higher in deep than superficial nephrons (78±2 v.s. 57±4 mm Hg). These findings strongly suggest the presence of abnormal renal hemodynamics, especially in the deep cortical region, in type 2 diabetes ; OLM may improve these abnormalities at the prediabetic stage.

预防或促进糖尿病肾病发展的机制仍不清楚。在 2 型糖尿病大鼠中进行了研究，以调查 12 周龄 2 型糖尿病大鼠 (OLETF) 中肾脏血流动力学异常的存在情况和发病时间点。我们确定了被认为是糖尿病前期的大鼠和对照大鼠 (LETO) 的 AT1 受体拮抗剂奥美沙坦 (OLM; 5mg/kg) 对总 (RBF)、浅表的影响(SBF) 和深部肾皮质血流量 (DBF) 在 LETO 中显着增加，但在 OLETF 中没有。相反，OLM 对 LETO 中的 DBF 没有影响，但在 OLETF 中增加了 DBF。约 40 周龄的 OLETF 和 LETO 中的肾小球反馈 (TGF) 反应降低（7.3% vs 25.7%）。与年龄相当的大鼠相比，我们评估了夹住腹主动脉引起的肾灌注压（RPP）降低对 RBF、SBF 和 DBF 的影响，但 OLETF 和 LETO 大鼠的 SBF 没有显着变化，而 OLETF 大鼠的 DBF 降低显着更多。 OLETF 中的 LETO 反应降低（4.4% vs. 18.8%）。 (P_<gc>)。OLETF 中的 P_<gc> 深部肾单位显着高于浅表肾单位 (78±2 vs. 57±4 mm Hg)。这些发现表明存在异常的肾脏血流动力学，特别是在深部皮质区域。 ，在 2 型糖尿病中；OLM 可以改善糖尿病前期的这些异常。