The roles of endothelin and growth factors in ischemic acute renal failure.

内皮素和生长因子在缺血性急性肾衰竭中的作用。

• 批准号: 04670385
• 负责人: HISHIDA Akira
• 金额: $ 0.51万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670385/
• 关键词: acute renal failure; nephrectomy; endothelin; thromboxane; PCNA; 虚血性急性腎不全; イヌリンクリアランス

The roles of endothelin and thromboxane A2 in ischemic acute renal failure were evaluated in rats. A 60 min left renal artery occlusion induced a decrease in inulin clearance(Cin) in left kidney and histological changes including tubular necrosis and cast formation. Antecedent nephrectomy of right kidney attenuates the decrease in Cin and tubular necrosis at 48 hours after ischemia. The beneficial effects of right nephrectomy was associated with the attenuation of the increases in renal endothelin and thromboxane B2 contents. The treatment with monoclonal endothelin antibody(AwETN40) or endothelin A receptor antagonist(FR 139317) failed to attenuate the decline of Cin and histological changes in both right nephrectomized and sham nephrectomized groups. The doses that we used in this experiment was enough to inhibit the hypertensive effects of 1.2 nmol/kg of endothelin. In contrast, the inhibitor of thromboxane A2 synthesis(OKY 046) attenuated the ischemia-induced decreases in urine output, renal blood flow and Cin in sham nephrectomized rats. These results suggest that intrarenal action of thromboxane A2 but not of endothelin may play a key role in right nephrectomy-induced attenuation of ischemic acute renal failure.

本实验观察了内皮素（ET）和血栓素A_2（TXA_2）在大鼠缺血性急性肾功能衰竭中的作用。左肾动脉阻断60分钟后，左肾菊粉清除率（Cin）下降，并出现肾小管坏死和管型形成等组织学变化。缺血后48小时，预先切除右肾可减轻Cin的降低和肾小管坏死。右肾切除术的有益效果与肾内皮素和血栓素B2含量增加的衰减有关。内皮素单克隆抗体（AwETN 40）或内皮素A受体拮抗剂（FR 139317）治疗右肾切除组和假肾切除组的Cin下降和组织学变化均未减弱。我们在本实验中使用的剂量足以抑制1.2 nmol/kg内皮素的高血压效应。与此相反，血栓素A2合成抑制剂（OKY 046）减弱缺血诱导的减少尿量，肾血流量和Cin在假肾切除大鼠。这些结果表明，肾内作用的血栓素A2，而不是内皮素可能发挥关键作用，在右肾切除术引起的缺血性急性肾功能衰竭的衰减。

项目成果

加藤 明彦,菱田 明: "急性腎不全とエンドセリン(ET)" 日本腎臓学会誌.

加藤明彦 (Akihiko Kato)、菱田彰 (Akira Hishida)：“急性肾衰竭和内皮素 (ET)”，日本肾脏病学会杂志。

Kotoh A,Hishida A,Kobayashi S,Honda N: "The glomerular alterations in experimental oliguric and nonoliguric acute renal failure" Renal Failure. 15. 215-224 (1993)

Kotoh A，Hishida A，Kobayashi S，Honda N：“实验性少尿和非少尿急性肾衰竭中的肾小球改变”肾衰竭。

Katoh A, Hishida A, Kobayashi S, Honda N.: "The glomerular alterations in experimental oliguric and nonoliguric acute renal failure." Renal Failure. 15-2. 215-224 (1993)

Katoh A、Hishida A、Kobayashi S、Honda N.：“实验性少尿和非少尿急性肾衰竭的肾小球改变。”

Honda N,Hishida A: "Pathophysiology of experimental nonoliguric acute renal failure" Kidney International. 43. 513-521 (1993)

Honda N，Hishida A：“实验性非少尿性急性肾衰竭的病理生理学”肾脏国际。

Honda N, Hishida A.: "Pathophysiology of experimental nonoliguric acute renal failure." Kidney International. 43. 513-521 (1993)

Honda N、Hishida A.：“实验性非少尿性急性肾衰竭的病理生理学”。