PLASMA LEVELS OF UROTENSIN II AND ITS URINARY EXCRETION IN PATIENTS WITH DIABETES MELLITUS : RELATION WITH DIABETIC NEPHROPATHY

尾加压素II(UII)是迄今发现的最有效的血管收缩多肽。UII的血管收缩作用比内皮素-1和血管紧张素II强一个数量级。为了阐明UII在器官损害发展过程中的病理生理作用，我们检测了不同器官的UII水平、尿液UII排泄量和UII的mRNA表达。结果：1.我们建立了一种针对人UII的放射免疫分析方法，并检测了各种疾病患者的血浆UII水平。慢性肾功能衰竭患者血浆UII水平升高(《柳叶刀》2001)。2型糖尿病患者的血浆UII水平也升高(Clin Sci 2003)。尿检显示，糖尿病本身是导致血浆UII水平升高的一个因素，而肾功能衰竭而不是蛋白尿是另一个导致血浆UII水平升高的单独因素(肽2004(出版))。心力衰竭患者和继发于内分泌疾病如嗜铬细胞瘤、原发性醛固酮增多症和库欣综合征的高血压患者血浆UII水平也升高。2.UII mRNA不仅在脑中表达，而且在人和大鼠的各种外周器官中也有表达。3.我们检测了5/6肾包块切除或冠状动脉结扎后急性心肌梗死大鼠心脏和肾脏UII mRNA的表达。4.低氧使培养的人内皮细胞UII mRNA表达增加，提示UII在肾脏缺血性损伤的进展中起重要作用。5.UII对培养的人肿瘤细胞具有增殖作用(Clin Sci 2002)。

Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. The potency of the vasoconstriction of UII is an order of magnitude greater than that of endothelin-1 and angiotensin II. In order to clarify the pathophysiological role of UII in the progression of organ damages, we examined plasma UII levels, urinary excretion of UII, and mRNA expression of UII in various organs.Results:1.We newly developed a radioimmunoassay specific to human UII, and examined plasma UII levels in patients with various diseases. Plasma UII levels were elevated in patients with chronic renal failure (Lancet 2001). Patients with type-2 diabetes mellitus also had elevated plasma UII levels (Clin Sci 2003). Urinary examination showed that diabetes itself was a factor to elevate plasma UII levels and the renal failure, not proteinuria, was another isolated factor to increase plasma UII levels (Peptides 2004 (in press)). Patients with heart failure and those with hypertension secondary to endocrine diseases such as pheochromocytoma, primary aldosteronism and Cushing syndrome also had increased plasma UII levels.2.UII mRNA was expressed not only in brain but also in the various peripheral organs of humans and rats.3.We examined UII mRNA expression in hearts and kidneys of rats with 5/6 renal mass ablation or acute myocardial infarction after coronary ligation.4.Expression of UII mRNA in cultured human endothelial cells was increased by hypoxia, suggesting that UII has an important roles the progression of renal ischemic injury.5.UII has a proliferative effect on cultured human tumor cell lines (Clin Sci 2002).