GP130在压力超负荷性大鼠心肌中的表达变化及替米沙坦干预影响

Changes of expression of GP130 and the effect of Telmisartan in myocardium in pressure overload rats

目的观察糖蛋白130(GP130)9在压力超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周造成压力负荷性心肌肥厚模型,随机分为左室肥厚组(LVH)和替米沙坦组(Telmisartan,Tel),另设8只作为假手术组(Sham)。替米沙坦组灌胃给药(3mg·kg-·1d-1),连续4周。测定血流动力学指标和心室质量指数,放免法测定心肌血管紧张素Ⅱ(AngⅡ)含量,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<0.05),LVMI和RVMI亦明显升高(P<0.05);心肌组织AngⅡ含量和GP130蛋白表达水平明显增加(P<0.05￣0.01)。相关分析表明,心肌组织中GP130的蛋白表达与AngⅡ水平及LVMI呈显著正相关(P<0.05￣0.01)。替米沙坦改善血流动力学指标(P<0.05￣0.01),降低LVMI和RVM(IP<0.05),AngⅡ含量显著降低(P<0.01),GP130蛋白表达明显下降(P<0.05)。结论压力超负荷性大鼠心肌中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还可能与抑制GP130蛋白的过度表达相关。

Objective To determine the changes of expression of GP130 in myocardium in pressure overload rats and the relationship between the changes and ventricular remodeling in the rat, also to evaluate the effect of telmisartan on GP130 expression. Methods The 20 male SD rats were randomly divided into 2 groups for two weeks after partial hgating aorta： 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. Telmisartan group were dehvered by direct gastric gavage（3mg·kg^-1· d^-1） for 4 weeks. SBP,DBP and MABP were monitored by biological-signal image analyrzer system. LVMI and RVMI were Calculated. Ang Ⅱ level in myocardium was measured by radioimmunoassay. The protein level of GP130 of cardiomyocytes was determined by immunohistochemistry analysis. Results Compared with sham-operated group, hemodynamic parameters such as SBP,DBP and MABP were all significantly enhanced （P〈0.05）. LVMI and RVMI were increased （P〈0.05）. Ang Ⅱ level and the protein expressing of gp130 in cardiac tissue were significant enhanced （P〈0.05～0.01）. Correlated analysis found that there were significant positive correlations among GP130 protein level, myocardial Ang Ⅱ level and LVMI parameters （P〈0.05～0.01）. Telmisartan improved hemodynamics, decreased Ang Ⅱ level （P〈0.01）,LVMI and RVMI（P〈0.05）, decreased GP130 expression. （P〈0.05）. Conclusion Overexpressed of GP130 may play an important role in ventricular remodeling in hypertrophied rats, the mechanisms of telmisartan in preventing ventricular remodehng may be partly depress overexpression of GP130.