β3肾上腺素能受体通过降低钙敏感性介导正常和心衰大鼠心脏的负性肌力作用  

Activation of β3-adrenergic receptor mediated negative inotropic action through decreasing calcium sensitivity of rat ventricular myocytes

作　　者：杨岚[1] 李海清[1] 李晓鹏[1] 赵倩倩[1] 吴博威[1] 崔香丽[1] 

机构地区：[1]山西医科大学生理学系,山西省太原市030001

出　　处：《中国心血管病研究》2015年第7期659-664,671,672,共8页Chinese Journal of Cardiovascular Research

基　　金：山西省自然科学基金（项目编号：2012011040-8）;2011山西医科大学科技创新基金（项目编号：057514）;2013中央财政支持地方项目基金

摘　　要：目的探讨β3上腺素能受体在正常和心衰大鼠心脏中的作用机制。方法100只（SD）大鼠（体重180-220g）随机分成假手术组（30只）和心脏衰竭组（70只），结扎冠状动脉制成心衰模型，4周后假手术组和心衰组再随机分为β3体激动剂BRL37344组和β3体拮抗剂SR59230A组进行实验。结果与假手术组相比：①4周、8周、12周后心衰组大鼠心质量指数HW／BW（心重／体重）和LVW／BW（左心重／体重）均明显升高（P〈0．05），左室舒张末期内径（LVEDD）和左室收缩末期内径（LVESD）均明显增大（P〈0．05），左室射血分数（LVEF）和短轴缩短率（LVFS）均明显减小（P〈0．05）。②阻断β1、β2受体给予良受体激动剂BRL37344后，心衰组的心率（HR）、左心室收缩压（LVSP）、左室等容收缩期室内压最大上升速率（＋dp／dtmax）及左室等容舒张期室内压最大下降速率（-dp／dtmax）均下降（P〈0．05），左心室舒张压（LVEDP）升高（P〈0．05）；阻断β3受体后以上心功能检测指标明显改善。③心衰大鼠的左心室壁B3受体表达增加。④急性分离的单个心衰大鼠心肌细胞，给予BRL37344后肌小节收缩幅度（b1％peakh）、钙瞬变（F340／380）幅度均明显下降（从0．33±0．09到0．25±0．07，P=-0．074），钙敏感性降低（P〈0．05）。结论心衰大鼠心脏β3体表达显著增加。阻断β1和β2肾上腺素能受体的情况下给予BRL37344，大鼠离体心脏功能受到抑制；心衰大鼠给予BRL37344后负性肌力作用更明显。激动β3受体使心肌细胞收缩幅度和钙瞬变幅度下降，钙敏感性降低。Objective To observe the mechanism underlying the activation of β3-adrenoceptor（ β3 AR ） in normal and heart failure （HF） rats. Methods 100 SD rats （weighting 180-220 g）were randomly divided into sham group （n=30） and HF group （n=70）. Rat models were established by coronary artery ligation. After 4 weeks of surgery, Sham group and HF group were randomly divided into BRL37344 treated and SR59230A treated groups. Results Compared with the sham group. （1）After 4, 8 and 12 weeks the index of ventricular HW/BW and LVW/BW were significantly decreased （P〈0.05）. Left ventricular end-diastolic diameter （LVEDD） and left ventricular end-systolic diameter（LVESD） were significantly increased （P〈0.05）, left ventrieular ejection fraction （LVEF） and fractional shortening（LVFS） were significantly decreased（P〈0.05 ）. （2）After blockade of β1 and β2 re- ceptors as well as activing β3 receptors, the heart rate （HR）, left ventricular systolic pressure （LVSP）, left yen-trieular systolic isovolumic ventricular pressure maximal rate of rise （＋dp/dtmax） and left ventricular isovolumic re- laxation pressure and maximal rate of decrease （-dp/dtmax） were significantly lowered（P〈0.05）, while left ventric- ular diastolic pressure （LVEDP） was increased （P〈0.05）. After blockade of β3 receptor, hemodynamic parameters were reversed. （3）The expression of β3 receptors in the left ventricular wall increased in the HF rats after 4, 8 and 12 weeks of the ligation surgery. （4）In the isolated single cardiomyocytes, the amplitude of sarcomere contraction （expressed as bl%peak h ） and calcium transient （expressed as /X Ca） decreased in presence of BRL 37344 in I-IF rats （from 0.33±0.09 of control to 0.25±0.07,P=0.074）. The calcium sensitivity decreased after β3 adrenoceptor activation. Conclusion While had very low expression in normal rat heart, β3-adrenoceptor had much higher ex- pression in HF hearts of rat. When blocking of β1

关 键 词：心力衰竭 β3 肾上腺素能受体 钙敏感性 

分 类 号：Q95-33[生物学—动物学] R541.6[医药卫生—心血管疾病]