摘要
目的观察吗啡对小鼠脑微血管内皮细胞内源性P-糖蛋白基因abcblb表达的影响及其NF—κB信号通路机制。方法NF—κB抑制剂PDTC预先孵育小鼠脑微血管内皮细胞bEnd-3，以1mg／ml吗啡或哌替啶刺激，然后收集细胞，四甲基偶氮唑盐比色法检测细胞活力，反转录-PCR法半定量检测abcb1b mRNA水平。结果吗啡或哌替啶不影响脑微血管内皮细胞细胞增殖活力。吗啡可引起小鼠脑微血管内皮细胞abcblb表达上调，其中8-48h上调达78％-192％，而哌替啶处理不影响脑微血管内皮细胞abcb1b表达。PDTC预先处理可抑制12h（132％vs．245％）和24h（181％vs．325％）吗啡处理所引起的小鼠脑微血管内皮细胞abcb1b表达上调。结论吗啡可诱导小鼠脑微血管内皮细胞内源性P-糖蛋白基因abcb1b的表达，NF—κB信号通路参与了吗啡诱导abcb1b表达的调控过程，此可能是一个新的吗啡耐受干预途径。
Objective To observe the effects of morphine on P-glyeoprotein gene expression of abcb1b in brain mierovaseular endothelial cells in mouse, and the role of nuclear factor-roB （NF-κB） signaling pathway in the morphine-induced up-expression of abcb1b. Methods The mouse brain microvaseular endothelial cell line （b.END3） was subjected to pre-incubation with NF-κB inhibitor PDTC 5 mmmol/L, and then to stimulation with morphine 1 mg/ml or pethidine 1 mg/ml. And then the b.END3 was collected and subjected to MTT for proliferation activity and RT-PCR for abeblb mRNA level. Results Morphine or pethidine did not affect proliferation activity of brain microvascular endothelial cells. Morphine 1 μg/ml stimulation for 24 h induced up-expression of abeb1b in bend3 with an increase of 78%-192% from 8 h to 48 h. However,pethidine had no impact on the expression of abcb1b in brain microvascular endothelial cells. PDTC can inhibit the effect of morphine for 12 h （ 132% vs. 245%） and for 24 h （ 181% vs. 325%）. Conclusion Morphine can induce up-expression of endogenous P-glycoprotein gene abcblb in mouse brain microvaseular endothelial cells. NF-κB signaling pathway is involved in the morphine-induced up-expression of abcblb gene. NF-κB signaling pathway may be a new interference pathway to morphine tolerance.
出处
《实用疼痛学杂志》
2016年第1期3-7,共5页
Pain Clinic Journal
