CAJ | 학술논문

目的观察β_3-肾上腺素能受体(β_3-AR)对心力衰竭大鼠心室肌细胞内静息Ca~(2+)浓度([Ca~(2+)]I)的调控及其转导途径.方法通过结扎冠状动脉前降支制备大鼠实验性心力衰竭模型,经典酶分离法分离心肌细胞,Fluo-3/AM染色,激光共聚焦显微镜观察B_3-AR兴奋剂BRL-37344以及合用PTX(Gi抑制剂)、L-NAME(NOS抑制剂)、Methylene blue (NO抑制剂)时对心室肌细胞内静息Ca~(2+)浓度的影响及其转导途径.结果在心力衰竭和正常对照大鼠,β_3-AR激动剂BRL37344(1 μmol/L)分别使心室肌细胞内[Ca~(2+)]I下调至用药前水平的59.4%、45.5%(P<0.05);在分别用L-NAME(10μmoI/L)、Methylene blue(10 μmol/L)、PTX(2μg/ml)阻断下,BRL37344(1μmol/L)使正常对照大鼠[Ca~(2+)]I分别下降10.1%、16.9%、15.4%,而在心力衰竭大鼠[Ca~(2+)]I分别下降16.9%、19.3%、11.7%.结论 β_3-AR激动剂可以使心室肌细胞内[Ca~(2+)]I下调,心力衰竭心肌下调程度较轻,其作用是通过PTX-NOS-NO转导.
목적 관찰β_3-신상선소능수체(β_3-AR)대심력쇠갈대서심실기세포내정식Ca~(2+)농도([Ca~(2+)]I)적조공급기전도도경.방법 통과결찰관상동맥전강지제비대서실험성심력쇠갈모형,경전매분리법분리심기세포,Fluo-3/AM염색,격광공취초현미경관찰B_3-AR흥강제BRL-37344이급합용PTX(Gi억제제)、L-NAME(NOS억제제)、Methylene blue (NO억제제)시대심실기세포내정식Ca~(2+)농도적영향급기전도도경.결과 재심력쇠갈화정상대조대서,β_3-AR격동제BRL37344(1 μmol/L)분별사심실기세포내[Ca~(2+)]I하조지용약전수평적59.4%、45.5%(P<0.05);재분별용L-NAME(10μmoI/L)、Methylene blue(10 μmol/L)、PTX(2μg/ml)조단하,BRL37344(1μmol/L)사정상대조대서[Ca~(2+)]I분별하강10.1%、16.9%、15.4%,이재심력쇠갈대서[Ca~(2+)]I분별하강16.9%、19.3%、11.7%.결론 β_3-AR격동제가이사심실기세포내[Ca~(2+)]I하조,심력쇠갈심기하조정도교경,기작용시통과PTX-NOS-NO전도.
Objective To observe the effect of β_3-adrenoceptor (AR) in regulating resting intracellular Ca_(2+) concentration of the ventricular myocytes and investigate the signaling pathway in rats with experimental heart failure. Methods Rat models of experimental heart failure were established by ligation of the anterior descending artery, and the myocytes were isolated by enzymatic digestion. The resting intracellular Ca~(2+) concentration was determined using laser scanning confocal microscopy (LSCM) in the cells stimulated with 1 μmol/L BRL37344 (a selective β_3-AR agonist) alone or in combination with PTX,L-NAME, or methylene blue. Result In the ventricular myocytes from normal control rats, BRL373444 reduced the resting intracellular Ca~(2+) concentration of by 45.5%, while the reduction increased to 59.4% in the cells from rats with heart failure. In combination with L-NAME (10 μmol/L), methylene blue (10 μmol/L), and PTX (2 μg/ml), BRL373444 caused a reduction in resting intracellular Ca~(2+) concentration of the ventricle myocytes from normal control rats by 10.1%, 16.9%, and 15.4%,respectively in control group, while the rate was 16.9%, 19.3%, and 11.7% in the heart failure group. Conclusion β_3-AR agonist can decrease the resting intracellular Ca~(2+) concentration of the ventricular myocytes, but the reduction is smaller in cells from rats with heart failure than in cells of normal rats. This effect is mediated through the PTX-NOS-NO pathway.