缺血再灌注损伤对大鼠肝细胞钙池操纵的钙通道电流的影响及药物拮抗  

Effects of 2-APB on store-operated Ca^(2+) channel currents of hepatocytes after hepatic ischemia/reperfusion injury in rats

作　　者：黄昌州 张宗明 裘法祖[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院普外科,湖北省武汉市430030 [2]清华大学第一附属医院普外科,北京市100016

出　　处：《世界华人消化杂志》2005年第6期739-742,共4页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.311270532教育部跨世纪优秀人才培养计划基金资助项目;教技函[2002]48号上海市教委"曙光计划"基金资助项目;No.02SG20~~

摘　　要：目的:研究缺血再灌注损伤对大鼠肝细胞活性和钙池操纵的钙通道电流(Isoc)的影响及钙通道阻滞剂(2- aminoethoxydiphenyl borane,2-APB)的拮抗作用. 方法:建立大鼠肝缺血再灌注损伤模型,应用全细胞膜片钳技术研究缺血再灌注损伤对大鼠肝细胞Isoc的影响及2-APB的拮抗作用. 结果:缺血再灌注组肝细胞Isoc为-1 058.0±223.3pA (n=8),假手术组为664.5±140.4pA(n:8),两组比较差异显著(P<0.05).20、40、60、80、100 μmol/L的2-APB分别使Isoc由给药前的-1 056.7±225.1PA下降至给药后的-853.7±225.1PA、-686.3±145.0pA、-534.4±120.4pA、-382.6±58.0pA、-272.9±51.1PA, 抑制率分别为19.2±6.2%、35.1±7.6%、49.44±9.9%、63.8±15.8%、74.2±16.5%:给药前后的Isoc比较有显著差异(n=8,P<0.05或P<0.01);2-APB的抑制作用呈浓度依赖性增强,其EC50为64.6±10.7 μmol/L. 结论:缺血再灌注损伤具有增加大鼠肝细胞的钙离子内流的作用,钙离子内流增加可能导致肝细胞钙超载,从而降低肝细胞的活性;2-APB对缺血再灌注损伤大鼠肝细胞的钙离子内流具有抑制作用,因此对缺血再灌注损伤的肝细胞起到保护作用.AIM: To study the effects of hepatic ischemia/reperfusion (I/R) injury on hepatocellular viability and store-operated calcium channel currents (Isoc) in freshly isolated rat hepatocytes, and the effects of (2-aminoethoxydiphenyl borane) 2-APB on Isoc of hepatocytes after hepatic ischemia/reperfusion injury in rats. METHODS: Rat hepatic ischemia and reperfusion injury model was established. Hepatocellular viabilities were determined by trypan blue exclusion assay. The effects of 2-APB on Isoc was investigated by whole-cell patch plamp technique. RESULTS: Ischemia/reperfusion injury significantly reduced hepatocellular viability and increased Isoc in hepatocytes. 2-APB(20, 40, 60, 80,100 μmol/L)induced a concentration-dependent decrease of Isoc with IC50 value of 64.6±10.7 μmol/L(n = 8). CONCLUSION: Ischemia/reperfusion injury can reduce hepatocellular viability, probably through increasing Isoc in hepatocytes. 2-APB has a protective effect on is-chemia/reperfusion-induced liver injury, probably though inhibiting Isoc.

关 键 词：缺血再灌注损伤 大鼠肝细胞 钙通道电流 药物拮抗 钙池 全细胞膜片钳技术 钙离子内流 mol/L 钙通道阻滞剂 肝缺血再灌注 肝细胞钙超载 拮抗作用 抑制作用 肝细胞活性 浓度依赖性 损伤模型 差异显著 0.05 EC50 保护作用 

分 类 号：R575[医药卫生—消化系统]