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.

防止或促进糖尿病性肾病发展的机制仍然不太了解。在2型糖尿病大鼠中进行研究，以研究肾脏血流动力学异常的存在和时间点。在被认为是糖尿病前期的12周大2型糖尿病大鼠（OLETF）中，我们确定了AT1受体拮抗剂Olmesartan（OLM; 5mg/kg）对总（RBF）（RBF），浅表（SBF）和深肾皮层血液（DBF）的影响。 Leto中OLM显着增加了SBF，但在OLETF中没有显着增加。相比之下，OLM对LETO中的DBF没有影响，但OLETF中的DBF增加了。微插入研究表明，在OLETF中，降低了细胞胶质细胞反馈（TGF）反应（7.3 V.S 25.7％）。在OLETF大约40周龄的OLETF和类似年龄的Leto中，我们评估了通过在RBF，SBF和DBF上夹紧腹主动脉引起的肾脏灌注压力（RPP）的可比降低的影响。 SBF在OLETF和LETO大鼠中没有显着变化，而DBF在OLETF中的改善远大于Leto。 OLETF中的TGF响应降低（4.4 V.S. 18.8％）。进行肾皮层切开术以测量肾小球毛细管压力（P_ <gc>）。在深层肾肾上腺（78±2 V.S. 57±4 mm Hg）中，OLETF中的P_ <gc>明显高得多。这些发现强烈表明存在异常的肾脏血流动力学，尤其是在深层皮质区域，在2型糖尿病中。 OLM可以在糖尿病阶段改善这些异常。