阿片类镇痛药对离体兔气管上皮纤毛摆动频率的影响(2)
芬太尼、舒芬太尼、瑞芬太尼是临床最常用的3种合成的苯基哌啶类镇痛药,其用药浓度也会因疾病、手术、患者身体状态的不同而有较大的差异,因此笔者选择3种药物的临床用药浓度,临床用药浓度×1/10以及临床用药浓度×10,用0.9%氯化钠溶液作为对照组,另外芬太尼、舒芬太尼及瑞芬太尼的三室模型半衰期如下[13],芬太尼:t1/2α1.8 min, t1/2β10~30 min,t1/2γ4~7 h;舒芬太尼:t1/2α17.7 min, t1/2β15~20 min,t1/2γ2.5 h;瑞芬太尼:t1/2α1 min, t1/2β4~17 min,t1/2γ1~1.6 h;因此我们选择了测量用药前(基础值),用药后20、40、60 min CBF。结果表明,芬太尼和舒芬太尼对CBF无影响,瑞芬太尼随浓度的增加,离体气管上皮纤毛摆动频率下降。本实验是在离体环境中进行的,人的呼吸系统处于复杂的环境之中,受到神经和体液因素的调节,对药物的反应是复杂的,同时,阿片药物的代谢受血浆蛋白结合率的影响,因此瑞芬太尼对患者气管上皮纤毛摆动频率的影响有待进一步研究。
, 百拇医药
瑞芬太尼降低气管上皮纤毛摆动频率的确切机制还不清楚。有研究显示气道黏膜内有阿片肽的结合位点[14],阿片肽对呼吸系统的影响可能涉及抑制性调节黏液分泌和基础CBF等方面,其作用主要是通过μ-受体介导的[2],瑞芬太尼是纯μ-受体激动剂[3],其对μ-受体的亲合力大于芬太尼和舒芬太尼, 这可能就是产生不同结果的原因。
综上所述,瑞芬太尼的临床用药浓度即可降低离体兔气管黏膜上皮纤毛摆动频率。
[参考文献]
[1] Braiman A,Priel Z. Efficient mucociliary transport relies on efficient regulation of ciliary beating[J]. Respir Physiol Neurobiol,2008,30:202-207.
[2] Elliott MK,Sisson JH,Wyatt TA. Effects of cigarette smoke and alcohol on ciliated tracheal epithelium and inflammatory cell recruitment[J]. Am J Respir Cell Mol Biol,2007,36(4):452-459.
, 百拇医药
[3] Elliott MK,Sisson JH,West WW,et al. Differential in vivo effects of whole cigarette smoke exposure versus cigarette smoke extract on mouse ciliated tracheal epithelium[J]. Exp Lung Res,2006,32(3-4):99-118.
[4] 印春铭,王俊科. 异丙酚和安氟醚对支气管粘液纤毛运输功能的影响[J]. 中华麻醉学杂志,2003,23(7):485-487.
[5] Padda GS,Kishioka C,Rubin BK. Propofol and methohexital have no significant effect on mocus secretion or clearance in the anesthetized dog [J]. Crit Care Med,2001,29(5):1045-1048.
, http://www.100md.com
[6] Karthinen P,Silvasli M,Saano V,et al. Effect of codeine on rat and guinea pig tracheal ciliary beat frequency [J]. Arzneimittelforschung,1991,41:1095-1097.
[7] Selwyn DA,Raphael JH, Lambert DG,et al. Effects of morphine on human nasal cilia beat frequency in vitro [J]. Br J Anaesth,1996,76:274-277.
[8] Iida H,Matsuura S,Shirakami G,et al. Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells [J]. Can J Anaesth,2006,53:242-249.
, http://www.100md.com
[9] 展新华,张锦,盛卓人. 一氧化氮信息传递系统对大鼠呼吸道纤毛运动的影响[J]. 中华麻醉学杂志,2000,20(3): 159-161.
[10] Salathe M. Regulation of mammalian ciliary beating [J]. Annu Rer Physiol,2007,69:401-422.
[11] Sisson JH, Pavlik JA, Wyatt TA. Alcohol stimulates ciliary motility of isolated airway axonemes through a nitric oxide, cyclase, and cyclic nucleotide-depend -ent kinase mechanism [J]. Alcohol Clin Exp Res,2009,33:610-616.
, http://www.100md.com
[12] Zhang L,Sanderson MJ. The role of cGMP in the regulation of rabbit airway ciliary beat frequency[J]. J Physiol, 2003,551: 765-776.
[13] 盛卓仁,王俊科. 实用临床麻醉学[M]. 4版. 北京:科学出版社,2009:155.
[14] Li DC, Shirakami G, Zhan XH, et al. Regulation of ciliary beat frequency by the nitric oxid oxide2cyclic guanosine monophosphate signaling pathway in rat airway epithelial cells [J]. Am J Respir Cell Mol Biol,2000,23: 175-181.
(收稿日期:2012-03-15 本文编辑:马 双), 百拇医药(王晓芳)
, 百拇医药
瑞芬太尼降低气管上皮纤毛摆动频率的确切机制还不清楚。有研究显示气道黏膜内有阿片肽的结合位点[14],阿片肽对呼吸系统的影响可能涉及抑制性调节黏液分泌和基础CBF等方面,其作用主要是通过μ-受体介导的[2],瑞芬太尼是纯μ-受体激动剂[3],其对μ-受体的亲合力大于芬太尼和舒芬太尼, 这可能就是产生不同结果的原因。
综上所述,瑞芬太尼的临床用药浓度即可降低离体兔气管黏膜上皮纤毛摆动频率。
[参考文献]
[1] Braiman A,Priel Z. Efficient mucociliary transport relies on efficient regulation of ciliary beating[J]. Respir Physiol Neurobiol,2008,30:202-207.
[2] Elliott MK,Sisson JH,Wyatt TA. Effects of cigarette smoke and alcohol on ciliated tracheal epithelium and inflammatory cell recruitment[J]. Am J Respir Cell Mol Biol,2007,36(4):452-459.
, 百拇医药
[3] Elliott MK,Sisson JH,West WW,et al. Differential in vivo effects of whole cigarette smoke exposure versus cigarette smoke extract on mouse ciliated tracheal epithelium[J]. Exp Lung Res,2006,32(3-4):99-118.
[4] 印春铭,王俊科. 异丙酚和安氟醚对支气管粘液纤毛运输功能的影响[J]. 中华麻醉学杂志,2003,23(7):485-487.
[5] Padda GS,Kishioka C,Rubin BK. Propofol and methohexital have no significant effect on mocus secretion or clearance in the anesthetized dog [J]. Crit Care Med,2001,29(5):1045-1048.
, http://www.100md.com
[6] Karthinen P,Silvasli M,Saano V,et al. Effect of codeine on rat and guinea pig tracheal ciliary beat frequency [J]. Arzneimittelforschung,1991,41:1095-1097.
[7] Selwyn DA,Raphael JH, Lambert DG,et al. Effects of morphine on human nasal cilia beat frequency in vitro [J]. Br J Anaesth,1996,76:274-277.
[8] Iida H,Matsuura S,Shirakami G,et al. Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells [J]. Can J Anaesth,2006,53:242-249.
, http://www.100md.com
[9] 展新华,张锦,盛卓人. 一氧化氮信息传递系统对大鼠呼吸道纤毛运动的影响[J]. 中华麻醉学杂志,2000,20(3): 159-161.
[10] Salathe M. Regulation of mammalian ciliary beating [J]. Annu Rer Physiol,2007,69:401-422.
[11] Sisson JH, Pavlik JA, Wyatt TA. Alcohol stimulates ciliary motility of isolated airway axonemes through a nitric oxide, cyclase, and cyclic nucleotide-depend -ent kinase mechanism [J]. Alcohol Clin Exp Res,2009,33:610-616.
, http://www.100md.com
[12] Zhang L,Sanderson MJ. The role of cGMP in the regulation of rabbit airway ciliary beat frequency[J]. J Physiol, 2003,551: 765-776.
[13] 盛卓仁,王俊科. 实用临床麻醉学[M]. 4版. 北京:科学出版社,2009:155.
[14] Li DC, Shirakami G, Zhan XH, et al. Regulation of ciliary beat frequency by the nitric oxid oxide2cyclic guanosine monophosphate signaling pathway in rat airway epithelial cells [J]. Am J Respir Cell Mol Biol,2000,23: 175-181.
(收稿日期:2012-03-15 本文编辑:马 双), 百拇医药(王晓芳)