糖尿病家兔心室肌细胞L型钙电流对模拟缺血-再灌注呈“钝化”反应(英文)  

Blunted response of L-type calcium current to simulated ischemia and reperfusion in ventricular myocytes from diabetic rabbits

作　　者：李健[1,2] 柳青[3] 李广平[1,2] 

机构地区：[1]天津医科大学第二医院心脏内科,天津300211 [2]天津心脏病学研究所,天津300211 [3]天津医科大学第二医院心脏外科,天津300211

出　　处：《中国病理生理杂志》2010年第11期2155-2160,共6页Chinese Journal of Pathophysiology

摘　　要：目的:评估分析模拟急性缺血-再灌注对糖尿病与正常家兔心室肌细胞L型钙通道电流(ICa,L)的作用。方法:采用四氧嘧啶静脉注射建立6周的糖尿病家兔模型,胶原酶分离家兔左心室肌细胞,以膜片钳全细胞模式记录糖尿病家兔和正常对照家兔心室肌细胞在基线状态,模拟缺血灌流5min和再灌注5min三个时相的ICa,L。结果:糖尿病组和对照组心室肌细胞最大ICa,L密度在基线状态无显著差异;对照组细胞(n=11)最大ICa,L密度在基线、缺血灌流后和再灌注后分别为(-8.36±1.63)pA/pF、(-5.90±1.75)pA/pF和(-4.22±1.02)pA/pF,缺血时ICa,L小于基线(P<0.01),而再灌注后ICa,L较之基线(P<0.01)和缺血时(P<0.05)均显著减小;糖尿病组细胞(n=9)最大ICa,L密度在基线、缺血灌流后和再灌注后分别为(-7.55±1.62)pA/pF、(-6.05±1.58)pA/pF和(-5.12±1.13)pA/pF,仅再灌注后ICa,L明显小于基线(P<0.01),而缺血时ICa,L分别与基线(P>0.05)和再灌注后(P>0.05)相比均无显著差异。结论:糖尿病状态下的心室肌细胞ICa,L对急性缺血损伤呈现"钝化"反应,随缺血进程的衰减较正常细胞缓慢,而缺血后再灌注则对于有无糖尿病的心肌均强力抑制ICa,L。本研究结果可能有助于提示糖尿病条件下的缺血-再灌注心肌损伤机制以及对合并缺血性心脏病的糖尿病患者的治疗方案。AIM： To evaluate the effects of simulated acute ischemia and reperfusion on L-type calcium current （ICa,L） in ventricular myocytes from diabetic and non-diabetic rabbits.METHODS： Using whole-cell patch clamp techniques, ICa,L was measured in left ventricular myocytes isolated from 6-week alloxan-induced diabetic rabbits and age-matched control ones at baseline, 5 min of simulated ischemia, and 5 min of reperfusion.RESULTS： There were no significant differences on baseline maximum ICa,L densities between diabetic and control ventricular myocytes. In control cells （n=11）, maximal ICa,L densities of baseline, ischemia and reperfusion were （-8.36±1.63）pA/pF, （-5.90±1.75）pA/pF and （-4.22±1.02）pA/pF, respectively. The ICa,L of ischemia was less than that of baseline （P〈0.01）, while the ICa,L of reperfusion was less than those of baseline （P〈0.01） and ischemia （P〈0.05）. In diabetic cells （n=9）,the ICa,L of baseline, ischemia and reperfusion were （-7.55±1.62）pA/pF, （-6.05±1.58）pA/pF and （-5.12±1.13）pA/pF, respectively. Only ICa,L of reperfusion was less than that of baseline （P〈0.01）, while ICa,L of ischemia was not significantly different from that of baseline （P〉0.05） or reperfusion （P〉0.05）.CONCLUSION： ICa,L in diabetic ventricular myocytes represents blunted response to acute ischemic injury, being decreased more slowly than that in control cells. Post-ischemic reperfusion is still a potent inhibitor against ICa,L in both diabetic and non-diabetic cells. This study may be indicative of the mechanism about ischemia-reperfusion injury to diabetic myocardium and the therapy for diabetic patients with ischemic heart disease.

关 键 词：糖尿病 缺血 再灌注 心室肌细胞 L-型钙电流 

分 类 号：R587.1[医药卫生—内分泌]