摘要
目的:探讨AT1受体抗体在心脏疾患发病中的作用,观察AT1受体抗体对大鼠心室肌细胞几种主要离子电流的影响。方法:按照人AT1受体细胞外第二环表位肽段合成AT1受体抗原肽段,以此肽段对大鼠进行主动免疫,获取抗AT1受体抗体;应用全细胞膜片钳技术,测定大鼠心室肌细胞L型Ca2+通道电流(ICa-L)、钠-钙交换电流(INa/Ca)、瞬时外向钾电流(Ito)与内向整流钾电流(IK1)。结果:抗AT1受体抗体IgG可剂量依赖性地增加ICa-L和INa/Ca,而减小Ito和IK1。以上各项指标与对照相比,均有显著差异。上述效应与AT1受体激动剂血管紧张素Ⅱ(AngⅡ)对这些电流的作用是一致的,并且可被AT1受体选择性拮抗剂氯沙坦所阻断。结论:心脏AT1受体抗体对心肌细胞离子电流具有显著的激动剂样效应,可以促进心肌细胞钙离子内流,而影响心脏的活动。这可能是该抗体参与心脏疾患发病的因素之一。
AIM ： In an attempt to clarify the role of anti - angiotensin Ⅱ - receptor antibody （ anti ATI - R Ab） in the pathogenesis of cardiovascular diseases, the effects of AT1 - R Ab on several major ionic currents in rat ventricular myocytes were studied. METHODS： The anti - AT1 - R Ab was derived by immunizing rats with synthetic peptide corresponding to the sequence of the second extracellular loop of human AT1 receptor. Whole cell patch clamp was used to measure the ionic currents including ICa-L , INa/Ca, Ito, and Ik1 in the rat ventrieular myocytes. RESULTS： AT1 - R Ab IgG significantly increased the Ica-L and INa/Ca but decreased the Ito and Ik1 in a dcse -dependent manner. Compared with the control, all these differences were statistically significant. These effects of anti - AT1 - R Ab were in the same way as the effects of Ang Ⅱ , an agonist of AT1 - R, and were blocked by losartan, a specific antagonist of AT1 - R. CONCLUSION： Anti - AT1 - R Ab displays remarkable agonist - like activity on the ionic currents in cardiomyocytes via stimulation of AT1 - R and increase of calcium influx, and therefore affects the cardiac activity. These findings indicate that AT1 - R Ab is involved in the pathogenesis of cardiovascular diseases.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2010年第11期2118-2123,共6页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.30900584)
四川省医学电生理重点实验室开放基金资助项目
