比索洛尔对心力衰竭大鼠IL-10、IL-18、细胞凋亡及相关蛋白表达的影响

Effect of bisoprolol on IL-10,IL-18,myocardial apoptosis and related protein expression in heart failure rats

目的比索洛尔对心力衰竭大鼠IL-10、IL-18、细胞凋亡及相关蛋白表达的影响。方法选取200~250 g SD大鼠48只,普通基础饲养2周后,按照相同的数目进行随机划分:假手术组、心衰模型组、比索洛尔治疗组三组,三个组别均为16只。术后第4周开始给予比索洛尔治疗组每日1次灌胃给药(日剂量:2.5 mg·kg^(-1)·d^(-1)),共8周。处理结束后,超声心动测定左室舒张末径(LVDS)、室收缩末径(LVDd),左室射血分数(LVEF),测定血清IL-10和IL-18的浓度,用western blot定量目的蛋白质。结果心衰组与假手术组比较,心衰组大鼠心功能明显降低,LVDS、LVDd明显扩大,LVEF、FS降低(P<0.05);IL-18明显升高,IL-10显著降低(P<0.01),Bcl-2/Bax显著降低(P<0.01)。比索洛尔治疗组与心衰组比较,比索洛尔治疗组心功能显著好转,LVDS、LVDd显著缩小,LVEF、FS升高(P<0.05);IL-10浓度升高,IL-18浓度降低(P<0.01);Bcl-2/Bax明显升高(P<0.01)。结论比索洛尔能使心衰大鼠心功能得到显著好转,其机制可能与改变炎性细胞因子水平,抑制细胞凋亡及相关蛋白表达有关。

Objective To investigate the effect of bisoprolol on inflammatory cytokines（ IL-10 and IL-18） and myocardial cell apoptosis and expression of related protein in rats with heart failure. Methods Selected48 SD rats weighted between 200 and 250 gram,fed with ordinary feed for two weeks,they were randomly divided into three groups with 16 rats in each Group： false operation group,heart failure model control group,and bisoprolol group. Rats in the bisoprolol group were intra-gastric administrated with bisoprolol（ daily dose： 2.5 mg·kg-1· d-1） since the 4 th week after surgery,last for 8 weeks. After the processing,use the Ultrasonic echocardiography to determine the LVDd,LVDS,LVEF. Detecting the content of the IL-10 and IL-18,and detected the protein by using western blot method. Results The rat cardiac function was obviously reduced in heart failure group compared with control group. The levels of LVDS and LVDd significantly expanded,the levels of LVEF and FS decreased（ P〈0. 05）. The levels of IL-18 elevated,and IL-10 dropped（ P〈0.01）. The levels of Bax elevated,and Bcl-2 dropped,Bcl-2/Bax dropped（ P〈0.01）. Compared to the heart failure group,cardiac function in bisoprolol group improved significantly. The levels of LVDS and LVDd significantly reduced. The levels of LVEF and FS increased（ P〈0. 05）. The levels of IL-18 dropped,and IL-10 elevated（ P〈0.01）. The levels of Bax dropped,Bcl-2 elevated,Bcl-2/Bax elevated（ P 0.01）. Conclusions Bisoprolol injection can improve cardiac function in heart failure rats and its mechanism may be related to the change of inflammatory cytokines and inhibit the myocardial apoptosis and the expression of apoptosis related proteins.