Wang Xiaoxia, Desai Kaushik, Clausen Jes Thorn, Wu Lingyun
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Kidney Int. 2004 Dec;66(6):2315-21. doi: 10.1111/j.1523-1755.2004.66034.x.
Methylglyoxal (MG), a metabolite of glucose, causes nonenzymatic glycation of proteins to form irreversible advanced glycation end products (AGEs). The role of MG in the development of essential hypertension is unknown, although MG has been extensively studied in relation to diabetes.
Blood pressure of spontaneously hypertensive rats (SHR) and paired Wistar Kyoto (WKY) rats was measured at 5, 8, 13, and 20 weeks of age. HPLC was used to determine the levels of plasma and kidney MG, as well as reduced or oxidized glutathione in the kidney. MG-induced AGEs, Nepsilon-carboxyethyl-lysine (CEL), and Nepsilon-carboxymethyl-lysine (CML) in the kidney were detected by immunohistochemistry. Glutathione peroxidase and reductase activities in the kidney were also determined.
Plasma MG levels were significantly elevated in SHR, but not in WKY rats, at 8, 13, and 20 weeks of age in parallel with blood pressure increase. Kidney MG levels in SHR were increased by 21% and 38% at 13 and 20 weeks, respectively, compared to age-matched WKY rats. There were no differences in blood pressure and MG levels in plasma and kidney between SHR and WKY rats at 5 weeks of age. Immunohistochemistry revealed more intense staining for CML and CEL in kidneys from SHR compared to WKY rats from 8 weeks onward. Most of the staining was localized to renal tubules with some staining in the glomerular vessels.
MG and AGEs formation was significantly elevated in kidney from SHR, which may cause local vascular and tubular damage, contributing to the development and complications of hypertension.
甲基乙二醛（MG）是葡萄糖的一种代谢产物，可导致蛋白质发生非酶糖基化反应，形成不可逆的晚期糖基化终产物（AGEs）。尽管MG已在糖尿病研究中得到广泛研究，但其在原发性高血压发病过程中的作用尚不清楚。
在5、8、13和20周龄时测量自发性高血压大鼠（SHR）和配对的Wistar Kyoto（WKY）大鼠的血压。采用高效液相色谱法测定血浆和肾脏中MG的水平，以及肾脏中还原型或氧化型谷胱甘肽的水平。通过免疫组织化学检测肾脏中MG诱导的AGEs、Nε-羧乙基赖氨酸（CEL）和Nε-羧甲基赖氨酸（CML）。同时还测定了肾脏中谷胱甘肽过氧化物酶和还原酶的活性。
在8、13和20周龄时，SHR的血浆MG水平显著升高，而WKY大鼠则未升高，且与血压升高平行。与年龄匹配的WKY大鼠相比，SHR在13周和20周时肾脏MG水平分别升高了21%和38%。5周龄时，SHR和WKY大鼠的血压以及血浆和肾脏中的MG水平没有差异。免疫组织化学显示，从8周龄起，SHR肾脏中CML和CEL的染色比WKY大鼠更强。大多数染色定位于肾小管，肾小球血管也有一些染色。
SHR肾脏中MG和AGEs的形成显著升高，这可能导致局部血管和肾小管损伤，促进高血压的发生和并发症。
