Nakamura Tsukasa, Matsuda Takaharu, Suzuki Yukiko, Ueda Yoshihiko, Koide Hikaru
Division of Nephrology, Department of Medicine, Misato Junshin Hospital, Saitama, Japan.
ASAIO J. 2003 Jul-Aug;49(4):430-4.
Low density lipoprotein (LDL) apheresis provides both structural and physiologic improvement to the vascular wall. The purpose of this study was to determine whether LDL pheresis alters levels of plasma matrix metalloproteinase-9 (MMP-9) and serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). MMP-9 and TIMP-1 were measured in 30 healthy control subjects (Group A), 20 type 2 diabetic hemodialysis patients without obvious arteriosclerosis obliterans (ASO) (Group B), and 20 type 2 diabetic hemodialysis patients with ASO (Group C). Hemodialysis patients were dialyzed three times weekly with a bicarbonate dialysate. Twelve Group C patients underwent LDL apheresis once weekly for 10 weeks, and changes in plasma MMP-9 and serum TIMP-1 levels because of LDL apheresis were measured. LDL apheresis resulted in a significant decrease in total cholesterol and LDL cholesterol levels (p < 0.01). In addition, LDL apheresis improved clinical symptoms (including cold lower extremity, intermittent claudication, and leg pain) and diminished the size of ulcer/necrosis in all patients. Plasma MMP-9 levels were significantly higher in Group C (76.5 +/- 14.6 ng/ml) than in Group A (31.2 +/- 8.4 ng/ml, p < 0.001) or Group B (58.5 +/- 10.8 ng/ml, p < 0.05). Serum TIMP-1 levels were significantly higher in Group C (360.5 +/- 116.5 ng/ml) than in Group A (142.5 +/- 82.5 ng/ml, p < 0.001) or Group B (254.6 +/- 92.6 ng/ml, p < 0.05). Plasma MMP-9 and serum TIMP-1 levels decreased significantly after LDL apheresis (p < 0.05). However, these levels showed little change in the remaining eight Group C patients who did not undergo LDL apheresis. The data suggested that MMP-9 and TIMP-1 are associated with ASO and that LDL apheresis is effective in reducing plasma MMP-9 and TIMP-1 levels in type 2 diabetic hemodialysis patients with ASO.
低密度脂蛋白（LDL）单采术可使血管壁在结构和生理方面均得到改善。本研究旨在确定LDL单采术是否会改变血浆基质金属蛋白酶-9（MMP-9）水平和血清基质金属蛋白酶组织抑制剂-1（TIMP-1）水平。对30名健康对照者（A组）、20名无明显闭塞性动脉硬化（ASO）的2型糖尿病血液透析患者（B组）以及20名患有ASO的2型糖尿病血液透析患者（C组）进行了MMP-9和TIMP-1检测。血液透析患者每周使用碳酸氢盐透析液进行3次透析。C组的12名患者每周进行1次LDL单采术，共进行10周，并检测LDL单采术导致的血浆MMP-9和血清TIMP-1水平变化。LDL单采术使总胆固醇和LDL胆固醇水平显著降低（p < 0.01）。此外，LDL单采术改善了所有患者的临床症状（包括下肢发冷、间歇性跛行和腿痛），并减小了溃疡/坏死的面积。C组的血浆MMP-�水平（76.5±14.6 ng/ml）显著高于A组（31.2±8.4 ng/ml，p < 0.001）或B组（58.5±10.8 ng/ml，p < 0.05）。C组的血清TIMP-1水平（360.5±116.5 ng/ml）显著高于A组（142.5±82.5 ng/ml，p < 0.001）或B组（254.6±92.6 ng/ml，p < 0.05）。LDL单采术后，血浆MMP-9和血清TIMP-1水平显著降低（p < 0.05）。然而，在其余8名未进行LDL单采术的C组患者中，这些水平几乎没有变化。数据表明，MMP-9和TIMP-1与ASO有关，且LDL单采术可有效降低患有ASO的2型糖尿病血液透析患者的血浆MMP-9和TIMP-1水平。
