The effects of intravenous anesthetics on aortic smooth muscle cells proliferation in vivo and in vitro

静脉麻醉药，如氯胺酮，已广泛用于心血管麻醉。然而，这些麻醉剂对血管平滑肌细胞增殖的影响知之甚少。本研究采用含5%胎牛血清的培养液培养大鼠主动脉平滑肌细胞，观察氯胺酮、异丙酚、利多卡因和芬太尼对大鼠主动脉平滑肌细胞增殖的影响。使用第二代至第三代的细胞。对于生长试验，测量麻醉剂对掺入细胞中的[^3H]-胸苷量和细胞计数的影响。用Student t检验或方差分析（ANOVA）进行统计学评价。氯胺酮（10-200 mM）以浓度依赖性方式抑制[^3H]-胸苷掺入培养的大鼠主动脉平滑肌细胞。然而，丙泊酚（100 mM），利多卡因（300 mM）和芬太尼（100 nM）在抑制主动脉平滑肌细胞增殖方面无效。氯胺酮在临床相关浓度下也可减少细胞数量。氯胺酮对大鼠主动脉平滑肌细胞增殖的抑制作用可被蛋白激酶C（PKC）抑制剂GF 109203 X阻断，提示氯胺酮通过PKC途径抑制大鼠主动脉平滑肌细胞增殖。

Intravenous anesthetics, such as ketamine, have been widely used for the cardiovascular anesthesia. However, the effects of these anesthetics on the vascular smooth muscle cell proliferations are poorly understood. In this study, we investigated the effects of ketamine, propofol, lidocaine and fentanyl on rat aorta smooth muscle cell proliferation.Rat aortic smooth muscle cells are cultured in medium containing 5% fetal calf serum. The cells at second to third passage were used. For growth assay, the effects of anesthetics on the amount of [^3H]-thymidine incorporated into the cells and cell counts were measured. Statistical evaluation was performed with Student's t-test or analysis of variance (ANOVA).Ketamine (10-200 mM) inhibited [^3H]-thymidine incorporation into rat cultured aorta smooth muscle cell in a concentration-dependent manner. However, propofol (100 mM), lidocaine (300 mM) and fentanyl (100 nM) were not effective at inhibition of aortic smooth muscle cells proliferations. Ketamine also decreased the cell number at clinical relevant concentrations. The inhibition of ketamine on aortic smooth muscle cells proliferations was abolished by protein kinase C (PKC) inhibitor, GF109203X.These findings suggest that ketamine inhibits proliferation of rat aortic smooth muscle cells proliferations via PKC pathway.