The mechanism and treatment of abnormalities about Renal Hemodynamic in the early stage diabetic.
The mechanism and treatment of abnormalities about Renal Hemodynamic in the early stage diabetic.
批准号:
17590814
负责人:
HASHIMOTO Seiji
金额:
$2.3万
依托单位:
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
项目状态:
已结题
起止时间:
2005 至 2006
中文摘要
预防或促进糖尿病肾病发展的机制尚不清楚。研究2型糖尿病大鼠肾脏血流动力学异常的存在及发生时间。在12周龄被认为是糖尿病前期的2型糖尿病大鼠(OLETF)和对照大鼠(LETO)中,我们测定了AT1受体拮抗剂奥美沙坦(OLM; 5mg/kg)对总(RBF)、浅(SBF)和深肾皮质血流量(DBF)的影响。OLM显著增加了LETO组的SBF,而OLETF组没有。相比之下,OLM对LETO的DBF没有影响,但增加了OLETF的DBF。微穿刺研究显示,OLETF降低了小管肾小球反馈(TGF)反应(7.3 vs . 25.7%)。在大约40周龄的OLETF和相当年龄的LETO中,我们评估了夹腹主动脉诱导的肾灌注压(RPP)相对降低对RBF、SBF和DBF的影响。OLETF大鼠和LETO大鼠的SBF均无显著变化,而OLETF大鼠的DBF明显低于LETO大鼠。OLETF组TGF反应降低(4.4 vs . 18.8%)。行肾皮质切除术测量肾小球毛细血管压力(P_<gc>)。OLETF深层肾单位P_<gc>明显高于浅表肾单位(78±2 vs . 57±4 mm Hg)。这些结果强烈提示2型糖尿病患者存在异常的肾脏血流动力学,特别是在深部皮质区;OLM可改善糖尿病前期的这些异常。
英文摘要
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.
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