NK-104，一种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，可降低大鼠主动脉平滑肌细胞的骨桥蛋白表达。

NK-104, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, reduces osteopontin expression by rat aortic smooth muscle cells.

Takemoto M, Kitahara M, Yokote K, Asaumi S, Take A, Saito Y, Mori S

Second Department of Internal Medicine, School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-0856, Japan.

Br J Pharmacol. 2001 May;133(1):83-8. doi: 10.1038/sj.bjp.0704046.

It has been suggested that osteopontin promotes the development of atherosclerosis, especially under diabetic conditions. 2. In the present study, we found that NK-104, a new potent synthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, reduced osteopontin expression both at protein and mRNA levels in cultured rat aortic smooth muscle cells. 3. The inhibitory effect of NK-104 was almost completely reversed by mevalonate, suggesting that mevalonate or its metabolites play important roles in the regulation of osteopontin expression. 4. Furthermore, oral administration of NK-104 (3 mg kg(-1) day(-1) for 7 days) effectively suppressed abnormally upregulated expression of osteopontin mRNA in the aorta and kidney of streptozotocin-induced diabetic rats. 5. These data support a notion that NK-104 is a suitable drug for the treatment of diabetic patients with hypercholesterolaemia.

有人提出骨桥蛋白会促进动脉粥样硬化的发展，尤其是在糖尿病情况下。2. 在本研究中，我们发现NK - 104，一种新型强效3 - 羟基 - 3 - 甲基戊二酰辅酶A还原酶抑制剂，在培养的大鼠主动脉平滑肌细胞中，在蛋白质和mRNA水平上均降低了骨桥蛋白的表达。3. 甲羟戊酸几乎完全逆转了NK - 104的抑制作用，这表明甲羟戊酸或其代谢产物在骨桥蛋白表达的调节中起重要作用。4. 此外，口服NK - 104（3毫克·千克⁻¹·天⁻¹，持续7天）有效抑制了链脲佐菌素诱导的糖尿病大鼠主动脉和肾脏中骨桥蛋白mRNA异常上调的表达。5. 这些数据支持这样一种观点，即NK - 104是治疗患有高胆固醇血症的糖尿病患者的合适药物。

NK-104, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, reduces osteopontin expression by rat aortic smooth muscle cells.