高胆固醇血症致大鼠心室肌细胞L-型钙电流失衡的机制  

Ionic mechanism underlying chance of L-type Ca^(2+) current in isolated rat ventricular myocytes induced by hypercholesterolemia

作　　者：吴红[1] 金秀东[2] 白云龙[1] 关立新[3] 吕延杰[1] 杨宝峰[1] 

机构地区：[1]哈尔滨医科大学药理学教研室,黑龙江哈尔滨150086 [2]牡丹江医学院生理学教研室,黑龙江牡丹江157011 [3]牡丹江医学院药理学教研室,黑龙江牡丹江157011

出　　处：《中国药理学通报》2008年第3期336-339,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金重点资助项目(No30430780);黑龙江省教育厅资助项目(No11511432)

摘　　要：目的研究高胆固醇血症(HC)对大鼠心室肌细胞L-型钙电流(ICa-L)以及细胞内钙浓度[Ca2+]i的影响。方法Wistar大鼠随机分为高胆固醇血症组和对照组各6只,分别给予高胆固醇饲料和普通饲料饲养4wk后,检测血脂;酶解法急性分离大鼠单个心肌细胞,采用全细胞膜片钳技术和激光扫描共聚焦显微镜观察高胆固醇血症对大鼠心室肌细胞ICa-L以及[Ca2+]i的变化。结果喂高胆固醇饲料4wk后,血清总胆固醇较正常对照组明显增高(P<0·01),甘油三脂无明显变化。膜片钳显示:高胆固醇血症大鼠各实验电压L-型钙电流电流密度均减少。在实验电压为0mV时,大鼠心室肌细胞L-型钙电流密度从正常对照组(-8·56±1·29)pA/pF减少到高胆固醇血症组(-5·24±0·90)pA/pF。激光共聚焦显示:在静息状态下,[Ca2+]i升高,峰值荧光强度由211·88±9·08增加至458·63±23·50(P<0·01)。结论高胆固醇血症可导致细胞内钙超载,使L-型钙通道电流失衡,可能是诱导心律失常的原因之一。Aim To investigate the effect of hyperchol- esterolemia on L-type Ca^2＋ （ICa-L） current and intracellular calcium concentration （ [ Ca^2＋ ] i ） in single ventricular myocytes of hypercholesterolemic rats. Methods 12 male wistar rats were randomly divided into two dietary groups： a group fed a normal diet （n = 6 ） and a group fed high-cholesterol diet （n = 6 ） for 4 weeks, respectively. The level of serum lipid was examined. Zymolytic method was used to isolate single ventricular myocytes from hypercholesterolemic and normal rats, which were loaded with Ca^2＋ -sensitive fluorescent indicator Fluo-3/AM. [ Ca^2＋ ]i represented by fluorescent intensity （ FI ） was measured by laser scanning confocal microscope. Whole cell patch clamp technique was used to record ICa-L. Results There was no significant influence exhibited on TG level. However,the serum total cholesterol（TC） level of hypercholesterolemic rats was much higher than that of model control group; at the test potential of 0 mV, /Ca-L decreased from （ - 8.56 ±1.29 ） pA/pF （ Control ） to （ - 5.24 ± 0. 90） pA/pF（HC） （n =6 in each group,P 〈0. 01 ） ; at resting levels, the peak value of fluorescent intensity was increased from 211.88 ± 9.08 to 458.63 ± 23.50 （ n = 6, P 〈 0. 01 ）. Conclusions Hypercholesterolemia affects the calcium currents and intracellular calcium concentration on cardiomyocytes of rats greatly, which may be the ionic mechanism of arrhythmia in- duced by hypercholesterolemia.

关 键 词：高胆固醇血症 心律失常 细胞浆内钙浓度 L-型钙电流 膜片钳技术 

分 类 号：R-332[医药卫生] R322.11