替米沙坦对高盐致大鼠主动脉重构中钠钾-ATP酶和钙-ATP酶的影响  

Effect of telmisartan on Na+-K+-ATPase and Ca2+-ATPase in aorta remodeling rats induced by high-salt

作　　者：刘婵 商黔惠 闵晓强 LIU Chan;SHANG Qian-hui;MIN Xiao-qiang(Hypertension Laboratory,Institute of Clinical Medicine and Institute of Cardiovascular Disease,The Affiliated Hospital of Zunyi Medical University,Zunyi 563003, Guizhou Province,China;Department of Cardiovascular,The Affiliated Hospital of Zunyi Medical University,Zunyi 563003, Guizhou Province,China)

机构地区：[1]遵义医科大学附属医院临床医学研究所、心血管病研究所高血压研究室,贵州遵义563003 [2]遵义医科大学附属医院心血管内科,贵州遵义563003

出　　处：《中国临床药理学杂志》2019年第14期1449-1452,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81160041; 81460077);贵州省优秀科技教育人才省长专项基金资助项目[黔省专合字(2012)15号]

摘　　要：目的研究钠-钾-ATP酶和钙-ATP酶对高盐饮食所致主动脉重构大鼠的影响和替米沙坦的干预效应。方法用4%高盐饮食喂养雄性Wistar大鼠诱导大鼠主动脉重构。按体重将大鼠随机分为3组:正常组、模型组和实验组,每组12只。正常组给予含0. 5%NaCl的正常盐饮食;模型组和实验组给予4%NaCl的高盐饮食;实验组在造模的同时给予替米沙坦,起始剂量为2 mg·kg^-1(根据血压情况每2周调整1次剂量至最大剂量为40 mg·kg^-1),连续24周。以免疫印迹法检测大鼠主动脉中膜的胶原Ⅲ型、钠-钾-ATP酶α2亚型和胞膜的钙-ATP酶亚型4(PMCA4)蛋白表达水平。结果正常组、模型组和实验组的胶原Ⅲ型蛋白相对表达量(OD值)分别为0. 58±0. 05,0. 81±0. 07和0. 59±0. 08;正常组、模型组和实验组的钠-钾-ATP酶α2蛋白相对表达量分别为0. 62±0. 09,0. 54±0. 10和0. 60±0. 08;正常组、模型组和实验组的PMCA4蛋白相对表达量分别为0. 41±0. 09,0. 30±0. 05和0. 42±0. 08。模型组与正常组比较,上述指标的差异均有统计学意义(均P <0. 05);实验组与模型组比较,上述指标的差异均有统计学意义(均P <0. 05)。结论钠-钾-ATP酶和钙-ATP酶活性以及蛋白表达下降可能参与高盐致血管重构的发生机制;替米沙坦通过增加钠-钾-ATP酶α2亚型和PMCA4表达来发挥抗主动脉重构作用。Objective To explore the role of sodium-potassium-ATPase( Na+-K+-ATPase) and calcium-ATPase( Ca2+-ATPase)in vascular remodeling induced by high-salt and the effect of telmisartan. Methods The aorta remodeling was induced by high-salt diet for 24 weeks in male Wistar rats. The rats were randomly divided into three groups: normal group,model group and experimental group,each group had 12 rats. Rats in normal group were fed with nomal-salt diet( 0. 5%NaCl). Rats in model group and experimental group were fed with high-salt diet( 4% NaCl),while rats in experimental group were simultaneously administered with telmisartan at the dose of initial dose was 2 mg·kg^-1( adjust dose to maximum dose of 40 mg·kg^-1 every 2 weeks according to blood pressure),for consecutive 24 weeks. The protein expression of Collagen type Ⅲ,Sodium-potassium-ATPase alpha 2 subtype( Na+-K+-ATPase α2) and plasma membrane Ca2+-ATPase 4( PMCA4) were determined by Western blotting. Results The Collagen type Ⅲ protein relative expression( OD value) in normol group,model group and experimental group were respectively0. 58 ± 0. 05,0. 81 ± 0. 07 and 0. 59 ± 0. 08;Na+-K+-ATPase α2 expression in the above three groups were respectively 0. 62 ± 0. 09,0. 54 ± 0. 10 and 0. 60 ± 0. 08;PMCA4 expression in the above three groups were respectively0. 41 ± 0. 09,0. 30 ± 0. 05 and 0. 42 ± 0. 08. Comparison between model group and normal group,the difference of the factors was significantly( all P < 0. 05);comparison between experimental group and model group,the difference of the factors was significantly( all P < 0. 05). Conclusion The decreased activity and protein expression of Na+-K+-ATPase and Ca2+-ATPase may be involved in the mechanism of aorta remodeling induced by high-salt diet.Telmisartan can play an anti-aortic remodeling role by increasing the expression of Na+-K+-ATPase α2 and PMCA4.

关 键 词：高盐饮食 主动脉重构 钠钾-ATP酶 钙-ATP酶 

分 类 号：R972[医药卫生—药品]