ASICs阻断剂对脑I/R大鼠神经行为学和梗死体积的影响Influence of ASICs blocker on ethology and infarct volume in rats after cerebral focal ischemia and reperfusion
展群岭,张小宁,呼海燕,李华
摘要(Abstract):
目的:探讨酸敏感离子通道(ASICs)阻断剂阿米洛利(amiloride)对脑缺血/再灌注(ischemia/reperfusion,I/R)大鼠神经行为学和梗死体积的影响。方法:参照ZeaLonga线栓法建立SD大鼠局灶性脑I/R模型。将32只大鼠随机分为4组,即假手术组、I/R模型对照组、amilorideⅠ组和amilorideⅡ组,每组8只,再灌注24h时间点行神经功能缺损评分,之后进行脑梗死灶体积测定和组织细胞HE染色。结果:I/R模型对照组神经功能缺损评分和脑梗死灶体积均明显大于amilorideⅠ组和amilorideⅡ组(P<0.05),amilorideⅠ组明显大于amilo-rideⅡ组(P<0.05)。结论:ASICs阻断剂amiloride对大鼠脑I/R损伤具有保护作用,其作用机制可能主要为amiloride阻断ASICs,抑制Ca2+超载,减轻脑I/R损伤。amiloride药理作用具有剂量效应关系。
关键词(KeyWords): 缺血再灌注损伤;酸敏感离子通道;阿米洛利
基金项目(Foundation):
作者(Author): 展群岭,张小宁,呼海燕,李华
参考文献(References):
- [1]Wahlgren NG,Ahmed N.Neuroprotectionin cerebral ischae mia:facts and fancies-the need for newapproaches[J].Cere brovasc Dis,2004,17(Suppl1):153-166.
- [2]Waldmann R,Champigny G,Lingueglia E,et al.H(+)-gate cation channels[J].Ann N Y Acad Sci,1999,868:67-76.
- [3]Xiong ZG,Zhu XM,Chu XP,et al.Neuroprotectioninische mia:blocking calcium-permeable acid-sensingion channels[J]Cell,2004,118(6):687-698.
- [4]Masereel B,Pochet L,Laeckmann D.An overview of inhibi-tors of Na(+)/H(+)exchanger[J].Eur J Med Chem,2003,38(6):547-554.
- [5]Longa Z,Weinstein PR,Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
- [6]Kittaka M,Wang L,Sun N,et al.Brain capillary tissue plas-minogen activator in a diabetes stroke model[J].Stroke,1996,27(4):712-719.
- [7]Tombaugh GC.Mild acidosis delays hypoxic spreading depres-sion andi mproves neuronal recovery in hippocampal slices[J].J Neurosci,1994,14(9):5635-5643.
- [8]Bianchi L,Driscoll M.Protons at the gate:DEG/ENaC ion channels help us feel and remember[J].Neuron,2002,34(3):337-340.
- [9]Waldmann R,Bassilana F,de Weille J,et al.Molecular clo-ning of a non-inactivating proton-gated Na+channel specific for sensory neurons[J].J Biol Chem,1997,272(34):20975-20978.
- [10]Yermolaieva O,Leonard AS,Schnizler MK,et al.Extracel-lular acidosis increases neuronal cell calcium by activating acid-sensingion channel1a[J].Proc Natl Acad Sci U S A,2004,101(17):6752-6757.
- [11]Tombaugh GC,Sapolsky RM.Evolving concepts about the role of acidosisinischemic neuropathology[J].J Neurochem,1993,61(3):793-803.
- [12]Scorza G,Minetti M.One-electron oxidation pathway of thi-ols by peroxynitrite in biological fluids:bicarbonate and a-scorbate promote the formation of albumin disulphide di mers in human blood plasma[J].Biochem J,1998,329(Pt2):405-413.
- [13]McDonald J W,Bhattacharyya T,Sensi SL,et al.Extracel-lular acidity potentiates AMPA receptor-mediated cortical neuronal death[J].J Neurosci,1998,18(16):6290-6299.
- [14]Kuribayashi Y,Itoh N,Kitano M,et al.Cerebroprotective properties of SM-20220,a potent Na(+)/H(+)exchange inhibitor,in transient cerebral ischemia in rats[J].Eur J Pharmacol,1999,383(2):163-168.