Mechanism of kidney protection effect of alpha-Melanocyte stimulating hormone in ischemia reperfusion injury.

α-黑素细胞刺激激素对缺血再灌注损伤的肾脏保护作用机制

• 批准号: 14571028
• 负责人: KOHDA Yukimasa
• 金额: $ 2.18万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571028/
• 关键词: alfa MSH; CYR61; acute renal failure

There was a dramatic up-regulation of rat CYR61 mRNA After 2 hours following bilateral renal ischemia, with decline by 4 hours. There was a slight CYR61 mRNA in normal lung, heart, skeletal muscle, and kidney, but not in liver. In normal animal, CYR61 mRNA abundance was highest in lung. After 4 hours following renal ischemia, CYR61 mRNA increased markedly in the kidney, but not in the other organs. CYR61 protein was increased at one hour, peaked at 4 to 8 hours, and still expressed 24 hours after ischemia. By in situ hybridization, CYR61 mRNA was detected at outer stripe of outer medulla, where the ischemia reperfusion injury is strongly observed. After renal ischemia, we collected urine and tried to detect CYR61 protein in it. CYR61 protein was detectable in urine following renal ischemia, but not in volume depression rat urine. These result suggest that CYR61 is regulating, in some pats, renal ischermia reperfusion injury, and may become a good marker for renal ischemic injury.In this study, I could not have other effect of alpha-MSH in bilateral renal ischemia reperfusion injury. During this study I found that Heparin-Binding Epithelial Growth Factor (HBEGF) was markedly increased 8 hours after renal ischemia. This HBEGF may work in renal recovery.

大鼠双侧肾缺血后2 h，CYR 61 mRNA表达显著上调，4 h后下降。CYR 61 mRNA在正常肺、心脏、骨骼肌和肾脏中有少量表达，但在肝脏中无表达。在正常动物中，CYR 61 mRNA丰度在肺中最高。肾缺血4 h后，肾脏CYR 61 mRNA表达明显增加，而其他脏器CYR 61 mRNA表达不明显。CYR 61蛋白在缺血后1h即开始表达，4 ~ 8h达高峰，24 h仍有表达。原位杂交结果显示，CYR 61 mRNA主要表达于缺血再灌注损伤较重的外髓外条。肾缺血后收集大鼠尿液，检测尿液中CYR 61蛋白，发现肾缺血后尿液中可检测到CYR 61蛋白，而容量减少大鼠尿液中则未检测到CYR 61蛋白。提示CYR 61在部分肾缺血再灌注损伤中起调节作用，可能成为肾缺血损伤的一个良好的标志物。在这项研究中，我发现肝素结合上皮生长因子（HBEGF）在肾缺血后8小时显著增加。这种HBEGF可能在肾脏恢复中起作用。

项目成果

T.Baba, H.Nonoguchi, K.Itoh, Y.Nakayama, Y.Kohda, T.Inoue, K.Tomita: "Gene Regulation of Renal Osmotic Stress-induced NaCl Organic Solute Cotransporter (ROSIT)."Nephron Experimental Nephrology. 96(3). 89-96 (2004)

T.Baba、H.Nonoguchi、K.Itoh、Y.Nakayama、Y.Kohda、T.Inoue、K.Tomita：“肾渗透压诱导的 NaCl 有机溶质协同转运蛋白 (ROSIT) 的基因调控。”肾单位实验肾病学。

T.Baba, H.Nonoguchi, K.Itoh, Y.Kohda, K.Tomita et al.: "Gene Regulation of Renal Osmotic Stress-induced NaCl Organic Solute Cotransporter (ROSIT)."Nephron Experimental Nephrology. 96(3). 89-96 (2004)

T.Baba、H.Nonoguchi、K.Itoh、Y.Kohda、K.Tomita 等人：“肾渗透压诱导的 NaCl 有机溶质协同转运蛋白 (ROSIT) 的基因调节”。肾单位实验肾病学。

H.Nonoguchi, S.Kiyama, H.Inoue, Y.Nakayama, T.Inoue, Y.Kohda, K.Machida, A.Tajima, K.Kitamura, T.Miyoshi, H.Shimada, H.Shimada, M.Tajiri, Y.Honda, M.Tanaka, K.Tomita: "Angiotensin-converting enzyme inhibitor withdrawal and ACE gene polymorphism."Clinical

H.Nonoguchi、S.Kiyama、H.Inoue、Y.Nakayama、T.Inoue、Y.Kohda、K.Machida、A.Tajima、K.Kitamura、T.Miyoshi、H.Shimada、H.Shimada、M.

Shiraishi N, Kitamura K, Kohda Y, K.Tomita et al.: "Increased endothelin-1 expression in the kidney in hypercalcemic rats."Kidney International. 63(3). 845-852 (2003)

Shiraishi N、Kitamura K、Kohda Y、K.Tomita 等人：“高钙血症大鼠肾脏内皮素 1 表达增加。”肾脏国际。

Y Kohda, Y Muramatsu, et al.: "Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury"Kidney International. 62(5). 1601-1610 (2002)

Y Kohda、Y Muramatsu 等人：“肾缺血再灌注损伤后尿液中富含半胱氨酸的蛋白 61（CYR61、CCN1）的早期检测”《肾脏国际》。