心肌营养素-1mRNA和糖蛋白130在压力超负荷性大鼠心肌中的表达变化及替米沙坦干预的影响  

Changes of expression of cardiotrophin-1 mRNA and glucoprotein 130 in myocardium in pressure overload rats and effect of Telmisartan

作　　者：余江恒[1] 宋碧辉 李法琦[2] 

机构地区：[1]自贡市第一人民医院心内科,643000 [2]重庆医科大学附属第一医院老年病科

出　　处：《中国心血管杂志》2013年第3期210-213,共4页Chinese Journal of Cardiovascular Medicine

摘　　要：目的观察心肌营养素-1(CT-1)和糖蛋白130(GP130)在压力超负荷性大鼠心肌中的表达变化与心室重构的关系,以及替米沙坦对心室重构及CT-1和GP130表达的影响。方法 20只雄性SD大鼠行腹主动脉缩窄术后2周制成压力负荷性心肌肥厚模型,随机分为左心室肥厚组(LVH)(10只)和替米沙坦组(Tel)(10只),另设8只作为假手术组(Sham)。替米沙坦组灌胃给药(3 mg.kg-1.d-1),连续4周。测定血流动力学指标和心室质量指数,放射免疫法测定心肌血管紧张素Ⅱ(AngⅡ)含量,原位杂交法检测心肌的CT-1 mRNA表达水平;免疫组化法检测心肌中GP130蛋白水平表达。结果与假手术组比较,肥厚组SBP、DBP和MBP显著升高(P=0.022,0.011,0.013),LVMI和RVMI亦明显升高(P=0.010,0.017);心肌组织AngⅡ含量、CT-1mRNA和GP130蛋白表达水平明显增加(P<0.01,P=0.032,0.021)。相关分析表明,心肌组织中CT-1mRNA和GP130的蛋白表达与AngⅡ及LVMI呈显著正相关(均为P<0.05)。替米沙坦改善血流动力学指标相比较肥厚组显著降低(P=0.041,0.021,0.019),降低LVMI和RVMI(P=0.038,0.042),血浆AngⅡ含量显著增加,心肌AngⅡ含量显著降低(均为P<0.01),CT-1mRNA和GP130蛋白表达明显下降(P=0.029,0.018)。结论压力超负荷性大鼠心肌中CT-1mRNA及其受体GP130蛋白的过度表达与心室重构的发生密切相关;替米沙坦逆转心室重构的机制可能与抑制CT-1及受体GP130蛋白的过度表达相关。Objective To determine the changes of expression of cardiotrophin-1 （ CT-1 ） mRNA and glucoprotein 130 （GP130）and their relationship with ventricular remodeling in myocardium in pressure overload rats, and to evaluate the effect of telmisartan on CT-lmRNA and GP130 expression. Methods The 20 male SD rats with two weeks after partial ligating aorta were randomly divided into two groups, hypertrophied group （LVH, n = 10） and telmisartan group （Tel, n = 10）. Sham-operated group （Sham, n = 8 ） was selected to serve non-partial ligating aorta. Tel group was treated with direct gastric garages （3mgokg-lod-1） for 4 weeks. SBP, DBP and MABP were monitored by biological-signal image analyzer system. LVMI and RVMI were calculated, and Ang I1 level in myocardium was measured by radioimmunoassay. The expression of CT-lmRNA in cardiomyocytes was determined with site hybridization histochemistry and the protein level of GP130 in cardiomyocytes determined by immune-histochemistry method. Results SBP, DBP, MABP, LVMI and RVMI in LVH group were significantly increased compared with sham-operated group （ all P 〈 0. 05 ） . Ang lI concentration, cardiotrophin-lmRNA gene expression and the protein expressing of GP130 in cardiac tissue in LVH group were also significantly increased than in sham-operated group （all P 〈 0. 05）. SBP, DBP, MABP, LVMI and RVMI in Tel group were significantly decreased compared with LVH group （ all P 〈 0. 05 ） , and plasma Ang lI was significantly increased and myocardial Ang 11 significantly decreased （P 〈 0. O1 ）, CT-1 mRNA and GP130 protein expression significantly decreased compared with LVH group （ P = 0. 029, 0. 018 ）. Conclusions Over- expressed cardiotrophin-1 gene and GP130 may contribute to ventricular remodeling in hypertrophied rats. Telmisartan could improve heart function of hypertrophied ventricular and reverse over-expression of cardiotrophin-1 gene and GP130 in myocardium. The mechanisms of telmisartan in preventing ventricular remodeling

关 键 词：心肌营养素-1 糖蛋白130 替米沙坦 心室重构 大鼠 

分 类 号：R965[医药卫生—药理学]