摘要
目的研究β3肾上腺素能受体激动剂BRL37344对心力衰竭(心衰)大鼠血液肿瘤坏死因子-α(TNF-α),血管紧张素Ⅱ(AngⅡ)及内皮素-1(ET-1)含量和心肌重构的影响,探讨β3AR在心衰中的作用。方法用异丙肾上腺素(ISO)诱导大鼠心衰,随机分为2组:心衰(CHF)组30只,BRL组35只,另设正常对照组25只。BRL组大鼠给予BRL-37344尾静脉注射,另外两组同时注射相应剂量的生理盐水。分别在2、6周时从各组选取存活大鼠8只检测TNF-α、AngⅡ、ET-1含量、心肌组织学变化和左室质量/体质量(LVW/BW)。结果①CHF组和BRL组大鼠血浆TNF-α、AngⅡ、ET-1均明显高于正常对照组(P<0.01),BRL组各项指标也明显高于CHF组(P<0.01);②病理组织学观察:HE染色和Mas-son染色均显示心衰大鼠心肌细胞破坏和胶原纤维组织增生明显;③LVW/BW:CHF组和BRL组LVW/BW明显高于对照组(P<0.01),而BRL组又高于CHF组(P<0.01)。结论BRL-37344能升高心衰大鼠血浆TNF-α、AngⅡ、ET-1含量,并且能促进左室重构,使心衰恶化。
Objective To explore the effect of BRL37344 (BRL), a kind of 153-adrenoceptor( 153-AR) agonist, on the plasma level of tumor necrosis factor-α( TNF-α, angiotension Ⅱ ( Ang Ⅱ ), endothelin-1 ( ET- 1 ) and the changes of cardiac tissue in histopathology in normal and progressive congestive heart failure (CHF) rats. Methods The model of heart failure in rat was induced by isoproterenol (ISO). The rats were randomly divided into three groups:control group (n = 25 ), CHF group (n = 30), BRL group (n = 35 ). BRL group received BRL 0.4 nmol·kg^-1·min^-1 through caudal vein for 10 min twice a week. The other groups received normal saline instead. The following indexes were evaluated at 2nd and 6th week : plasma level of TNF-α,Ang Ⅱ , ET-1 , histopathology by HE and Masson staining and the ratio of left ventricular weight to body weight (LVW/BW). Results As compared with control group, the plasma level of TNF-α, AngⅡ , ET-1 of CHF and BRL group were increased remarkably(P 〈0.01 ). There were necrotic myocardial cells and proliferative collagen fibers in heart failure rats, especially in BRL group. The ratio of LVW/BW in CHF group and BRL group were significantly increased than that of control group (P 〈 0.01 ) and the ratio of BRL group was also increased than that of CHF group (P 〈 0.01 ). Conclusion β3 -AR agonist aggravates cardiac function by increasing the plasma level of TNF-α, AngⅡ , ET-1 and progressing the necrosis of myocardial cells and the proliferation of collagen fibers .
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2005年第19期1939-1942,共4页
Journal of Third Military Medical University