Department of Pharmacy, Gan Su Province Hospital, Lan Zhou, China.
Pharmacology. 2013;91(3-4):123-30. doi: 10.1159/000346128. Epub 2013 Jan 23.
The association between diabetes and neointimal expansion after vascular injury has been attributed to the accumulation of advanced glycation end products (AGEs). Here we investigated the inhibitory effect of cariporide, a specific Na(+)/H(+) exchanger 1 blocker, on neointimal proliferation induced by AGEs in a balloon injury model.
Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP) was monitored by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. The level of reactive oxygen species (ROS) was determined by specific fluorescent probe. The phosphorylation of the nuclear factor-ĸB (NF-ĸB) system was studied by Western blot.
Cariporide significantly suppressed AGE-induced neointimal hyperplasia, vascular smooth muscle cell (VSMC) proliferation, COX-2, MMP-2 and MMP-9 expression. In addition, cariporide decreased AGE-induced ROS, malondiadehyde level and increased the superoxide dismutase and glutathione peroxidase activity. We also found that cariporide blocked AGE-induced NF-ĸB activation and inhibitor-ĸB degradation.
The results indicated that cariporide inhibited AGE-induced neointimal formation by suppressing the VSMC proliferation and the up-regulation of COX-2, MMP-2, MMP-9 via inhibiting ROS and NF-ĸB activation.
血管损伤后糖尿病与新生内膜扩张之间的关联归因于晚期糖基化终产物（AGEs）的积累。在这里，我们研究了特异性 Na(+)/H(+) 交换体 1 抑制剂 cariporide 对 AGE 诱导的球囊损伤模型中新生内膜增殖的抑制作用。
通过逆转录-聚合酶链反应（RT-PCR）和实时 PCR 监测环氧化酶-2（COX-2）和基质金属蛋白酶（MMP）的表达。通过特异性荧光探针测定活性氧（ROS）的水平。通过 Western blot 研究核因子-ĸB（NF-ĸB）系统的磷酸化。
cariporide 显著抑制了 AGE 诱导的新生内膜过度增生、血管平滑肌细胞（VSMC）增殖、COX-2、MMP-2 和 MMP-9 的表达。此外，cariporide 降低了 AGE 诱导的 ROS、丙二醛水平，并增加了超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。我们还发现 cariporide 阻断了 AGE 诱导的 NF-ĸB 激活和抑制剂-ĸB 降解。
结果表明，cariporide 通过抑制 ROS 和 NF-ĸB 激活，抑制 VSMC 增殖和 COX-2、MMP-2、MMP-9 的上调，抑制了 AGE 诱导的新生内膜形成。
