β_3受体激动剂BRL-37344促进大鼠心力衰竭及可能的作用机制  

Possible mechanism of β_3-adrenoceptor agonist(BRL-37344) aggravates heart failure in rats

作　　者：田颖[1] 李为民[1] 孔一慧[1] 

机构地区：[1]哈尔滨医科大学第一临床医学院心内科

出　　处：《基础医学与临床》2005年第6期517-520,共4页Basic and Clinical Medicine

基　　金：黑龙江省卫生厅资助项目(2002-036)

摘　　要：目的观察β3肾上腺素能受体激动剂(BRL37344)对血浆TNFα、AngⅡ和ET1水平及心肌重构的影响。方法用异丙肾上腺素(isoproterenol,ISO)诱导心力衰竭大鼠模型。随机分为心衰组(CHF)和BRL组,BRL组给予BRL37344尾静脉注射,同时另设对照组。结果2和6周时CHF组和BRL组大鼠血浆TNFα、AngⅡ、ET1均明显高于对照组(P<0.01),相同时间点BRL组ET1水平均高于CHF组(P<0.01),6周时BRL组AngⅡ也明显高于CHF组(P<0.01)。6周时BRL组上述指标均高于2周时水平(P<0.01),而CHF组只有TNFα高于2周时水平(P<0.05)。心衰大鼠心肌细胞破坏和胶原纤维组织增生明显,β3受体蛋白在心衰和应用BRL37344的大鼠心肌表达很明显。结论BRL37344能升高心衰大鼠血浆TNFα、AngⅡ和ET1含量,并且能促进左室重构,使心衰恶化。Objective To explore the effect of BRL-37344 (BRL),a kind of β_3-adrenoceptor(β_3-AR) agonist, on the plasma level of tumor necrosis factor-α(TNF-α)?angiotensionⅡ(AngⅡ)?Endothelin-1(ET-1)and myocardium remodeling of the rat with progressive congestive heart failure(CHF). Methods The model of heart failure was induced by isoproterenol (ISO). Then the rats were randomly divided into three groups: control group (n=25),CHF group (n=30) and BRL group (n=35).BRL groups received BRL 0.4 nmol/(kg·min) through caudal vein for ten minutes twice a week. The other groups received saline at the same time. Then evaluate the following indexes at the second and sixth week. The measurements included the plasma level of TNF-α?AngⅡ? ET-1 and histopathology (HE and Masson stain; immunohistochemical method). Results (1)Compared with control group, the plasma level of TNF-α?AngⅡ?ET-1 of CHF and BRL groups increased remarkably(all, P<0.01) at the second and sixth week. AngⅡ at the sixth week and ET-1 at both time also increased more significantly that in CHF group. At the sixth week, all indexes in BRL group increased than those at the second week and only TNF-α was increased at the same time in CHF group. (2) Histopathology: There were myocardial cells necrosis and collagen fibers proliferation in CHF group and BRL group and the latter is worse. On immunohistochemical method, β_3-adrenoceptor protein expresses more in heart failure rats compared with con-trol and CHF group. Conclusion β_3-AR agonist can aggravate cardiac function not only by increasing the plasma level of TNF-α?AngⅡand ET-1 but also by progressing myocardium remodeling stemed from myocardial cells necrosis and collagen fibers proliferation.

关 键 词：BRL-37344 心力衰竭 Β3受体激动剂 作用机制 血浆TNF-Α 肾上腺素能受体激动剂 AngⅡ ET-1水平 异丙肾上腺素 纤维组织增生 ET-1含量 尾静脉注射 CHF 心肌重构 大鼠模型 细胞破坏 大鼠心肌 心肌表达 受体蛋白 左室重构 

分 类 号：R541.6[医药卫生—心血管疾病]