Kimura I, Nagamori A, Honda R, Kobayashi S
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Immunopharmacology. 1998 Aug;40(2):105-18. doi: 10.1016/s0162-3109(98)00024-1.
The purpose of this study was to investigate the actions of intraperitoneal macrophages and aortic endothelial cells (EC) as the cause of proliferation of primary cultured smooth muscle cells (SMC) of the aorta in non-insulin-dependent diabetes mellitus (NIDDM) models, including spontaneously diabetic GK and streptozotocin-diabetic Wistar rats. Conditioned medium derived from macrophages of GK rats increased proliferation of SMC in Wistar rats to a greater extent when compared to normal Wistar rats in conditioned medium. Serum of both GK rats and of Wistar rats which was previously exposed to 16.7 and 25 mM glucose (glycated serum) activated normal macrophages, enhancing SMC proliferation. However, glycated serum and high concentrations of glucose did not affect directly the proliferation of SMC. Conditioned medium from EC of streptozotocin-Wistar rats enhanced SMC proliferation. The enhancing activity of EC in diabetic rats was mimicked by conditioned medium from glycated EC but not from EC treated with the diabetic rat serum nor glycated bovine serum albumin. Cholesterol (39 microg/ml) potentiated the action of glycated serum on macrophages, but neither the action of normal macrophages nor the direct action of SMC was affected. Both the actions of glycated serum and cholesterol were inhibited by a polyclonal platelet-derived growth factor-BB antibody. However, low density lipoprotein (LDL), acetylated LDL and oxidized LDL (25 microg/ml) did not potentiate the action of glycated serum. These results demonstrate that glycated serum in the NIDDM model predominantly activated macrophages, resulting in proliferation of SMC by the release of platelet-derived growth factor-BB. Cholesterol potentiated the actions of glycated serum on macrophages.
本研究旨在探讨腹腔巨噬细胞和主动脉内皮细胞（EC）在非胰岛素依赖型糖尿病（NIDDM）模型中作为主动脉原代培养平滑肌细胞（SMC）增殖原因的作用，该模型包括自发性糖尿病GK大鼠和链脲佐菌素诱导糖尿病的Wistar大鼠。与正常Wistar大鼠条件培养基相比，GK大鼠巨噬细胞来源的条件培养基能更大程度地增加Wistar大鼠SMC的增殖。GK大鼠和先前暴露于16.7和25 mM葡萄糖的Wistar大鼠的血清（糖化血清）激活正常巨噬细胞，增强SMC增殖。然而，糖化血清和高浓度葡萄糖并未直接影响SMC的增殖。链脲佐菌素-Wistar大鼠EC的条件培养基增强了SMC增殖。糖尿病大鼠EC的增强活性可被糖化EC的条件培养基模拟，但不能被糖尿病大鼠血清处理的EC或糖化牛血清白蛋白处理的EC模拟。胆固醇（39微克/毫升）增强了糖化血清对巨噬细胞的作用，但既不影响正常巨噬细胞的作用，也不影响SMC的直接作用。糖化血清和胆固醇的作用均被多克隆血小板衍生生长因子-BB抗体抑制。然而，低密度脂蛋白（LDL）、乙酰化LDL和氧化LDL（25微克/毫升）并未增强糖化血清的作用。这些结果表明，NIDDM模型中的糖化血清主要激活巨噬细胞，通过释放血小板衍生生长因子-BB导致SMC增殖。胆固醇增强了糖化血清对巨噬细胞的作用。
