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尚不清楚。在2型糖尿病大鼠中进行研究，以调查肾脏血流动力学异常的存在和发病时间点。在12周龄被认为是糖尿病前期的2型糖尿病大鼠(OLETF)和对照组大鼠(LETO)上，我们测定了AT1受体拮抗剂奥美沙坦(OLM；5 mg/kg)对总(RBF)、肾浅层(SBF)和肾深部皮质血流量(DBF)的影响。OLM使LETO患者SBF显著增加，而OLETF患者SBF增加不明显。相反，OLM对LETO的DBF没有影响，但增加了OLETF的DBF。微穿刺术显示OLETF患者的肾小管球反馈反应降低(7.3vs25.7%)。在约40周龄的OLETF和同龄的LETO中，我们评估了通过夹闭腹主动脉而导致的肾灌注压(RPP)的类似降低对RBF、SBF和DBF的影响。OLETF和LETO大鼠的SBF均无明显变化，但OLETF的DBF下降幅度明显大于LETO。OLETF组转化生长因子反应减少(4.4vs.18.8%)。肾皮质切开术测量肾小球毛细血管压(P&lt；GC&gt；)。OLETF深部P&lt；GC&GT；显著高于浅层肾(78±2vs.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，特别是在皮质深部；OLM可能在糖尿病前期改善这些异常。