Lin C R, Cheng J T, Lin F C, Chou A K, Lee T C, Chen J T, Yang L C
Anesthesiology Research Laboratory, Kaohsiung Chang Gung Memorial Hospital, Taiwan, Niao-Shung Hsiang.
Cell Biol Toxicol. 2002;18(1):63-70. doi: 10.1023/a:1014423330210.
Neurotoxicity is the dose-limiting side-effect of vincristine in cancer therapy. Using the nerve growth factor (NGF)-dependent neurite outgrowth and cell proliferation of the PC12 pheochromocytoma cell line as an in vitro assay, the protective effect of different intravenous anesthetics was assessed. Vincristine (1 nmol/L) significantly decreased the percentage of neurite-forming cells from 68% +/- 9% to 27% +/- 7% within a 3-day incubation period. The longer neurites (> 2 x cell body) in particular proved to be extremely sensitive to vincristine (from 17% +/- 4% to 0% of total neurite-expressing cells). Flow cytometry results revealed an S-phase percentage of 15.85% +/- 3.25% after NGF induction, with vincristine reducing this percentage to 0.68% +/- 0.38%. Reversal of the inhibitory effect of vincristine was noted in the cells treated with thiopental or propofol but not etomidate. Bicuculline partially antagonized the protective effect of thiopental and propofol in both studies. We conclude that thiopental and propofol, but not etomidate, have a protective effect in vincristine-induced neurotoxicity. The protective effect produced by thiopental and propofol is probably secondary to activation of GABAA receptors.
神经毒性是长春新碱在癌症治疗中的剂量限制性副作用。利用依赖神经生长因子（NGF）的PC12嗜铬细胞瘤细胞系的神经突生长和细胞增殖作为体外试验，评估了不同静脉麻醉药的保护作用。在3天的孵育期内，长春新碱（1 nmol/L）显著降低了形成神经突的细胞百分比，从68%±9%降至27%±7%。特别是较长的神经突（>2×细胞体）对长春新碱极为敏感（从表达神经突的细胞总数的17%±4%降至0%）。流式细胞术结果显示，NGF诱导后S期百分比为15.85%±3.25%，长春新碱将该百分比降至0.68%±0.38%。在用硫喷妥钠或丙泊酚处理的细胞中观察到长春新碱抑制作用的逆转，但依托咪酯处理的细胞未出现这种情况。在两项研究中，荷包牡丹碱部分拮抗了硫喷妥钠和丙泊酚的保护作用。我们得出结论，硫喷妥钠和丙泊酚对长春新碱诱导的神经毒性有保护作用，而依托咪酯则没有。硫喷妥钠和丙泊酚产生的保护作用可能继发于GABAA受体的激活。
