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研究以调查肾血流动力学异常的存在和发作时间点。在12周龄2型糖尿病大鼠（OLETF）（被认为是糖尿病前期）和对照大鼠（LETO）中，我们测定了AT 1受体拮抗剂奥美沙坦（OLM; 5 mg/kg）对总（RBF）、浅表（SBF）和深层肾皮质血流量（DBF）的影响。在LETO中，OLM显著增加SBF，但在OLETF中没有。相反，OLM对LETO的DBF没有影响，但增加了OLETF的DBF。微穿刺研究表明，肾小管肾小球反馈（TGF）反应减少在OLETF（7.3 vs25.7%）。在约40周龄的OLETF和年龄相当的LETO中，我们评估了通过夹闭腹主动脉诱导的肾灌注压（RPP）的可比降低对RBF、SBF和DBF的影响。OLETF和LETO大鼠的SBF均无显著变化，而OLETF大鼠的DBF下降幅度明显大于LETO大鼠。在OLETF中TGF应答降低（4.4 vs. 18.8%）。肾皮质切开术测定肾小球毛细血管压（P_<gc>）。深<gc>肾组OLETF的P_（78±2）显著高于浅肾组（P &lt;0.05）。57±4 mm Hg）。这些发现强烈提示2型糖尿病患者存在肾脏血流动力学异常，特别是在深层皮质区域; OLM可能在糖尿病前期改善这些异常。