长期容量超负荷心力衰竭大鼠心脏交感神经去甲肾上腺素转运蛋白表达的变化  

Alterations of cardiac sympathetic norepinephrine transporter expression in rats with volume overload

作　　者：李贺[1] 胡小萍 麻荪凯 费俭[3] 张国元[1] 吴宗贵[1] 

机构地区：[1]上海长征医院心内科,上海200003 [2]上海浦南医院病理科,上海200125 [3]中国科学院上海细胞生物学研究所,上海200031

出　　处：《中国病理生理杂志》2001年第12期1163-1167,共5页Chinese Journal of Pathophysiology

基　　金：上海市科委博士后基金资助项目 (No .98- 10 )

摘　　要：目的 :检测长期容量超负荷 (VOL)条件下大鼠心肌 β1-肾上腺素能受体 ( β1-AR)及其上游调控因素心脏交感神经去甲肾上腺素转运蛋白 (NET)mRNA表达的变化。方法 :用RT -PCR及Northern杂交检测心脏交感神经NET表达组织特异性、VOL后不同时间大鼠心脏交感神经NET及 β1-ARmRNA表达水平变化。结果 :①心脏交感神经节专一性表达心脏交感神经NET基因。②VOL后 3d大鼠左心室收缩压 (LVSP)下降最显著 ( 2 4 % ) (P <0 0 5 ) ,此后逐渐增高 ,至手术后 60d高于对照组 3 2 8% (P <0 0 5 ) ;3 - 3 0d舒张末压 (LVEDP)显著增高 177 96% -2 3 4 75 % (P <0 0 5 ) ,术后 60d恢复至对照组水平 (P >0 0 5 )。③与对照组比较VOL大鼠术后 3 - 3 0dNET、β1-ARmRNA表达无下降 (P >0 0 5 ) ,60dNETRT -PCR及Northern杂交检测分别显示下降 4 3 3 % (P <0 0 5 )和 63 5 % (P <0 0 5 ) ,Northern杂交显示 β1-AR下降 5 0 % (P <0 0 5 )。结论 :长期心脏VOL大鼠左心室 β1-ARmRNA可维持较长时间稳定与心脏交感神经NETmRNA表达相对稳定有关。NET表达正常对维持 β1-AR对肾上腺素能刺激的敏感性 。AIM: To determine the alterations of myocardial β 1-adrenergic receptor (β 1-AR) and cardiac sympathetic norepinephrine transporter (NET) mRNA expression, which is upstream modulator of β 1-AR, in rats with longterm volume overload (VOL).METHODS: Left ventricular systolic (LVSP) and end diastolic pressure (LVEDP) of rats with VOL induced by aortacaval fistula operation and control group were measured at 3, 14,30 and 60 d after the operation, the mRNA at the time points was measured by RT-PCR and Northern blot analysis and quantified by densitometry.RESULTS: The cardiac sympathetic NET specific expression is in the cardiac sympathetic ganglia. Be compared with the control group, LVSP of VOL rats decreased most dramatically by 24%( P <0 05) at 3d, after that LSVP increased gradually and were higher than control group at 60 d. LVEDP increased initially compared with the control ( P <0 05), the latter recovered to the control levels. RT-PCR and Northern blot showed that in VOL rats the NET mRNA did not decreased significantly from 3 to 30 d, and decreased remarkably at 60 d after the operation ( P <0.05). The pattern of β 1-AR mRNA expression were similar to the NET.CONCLUSIONS: The results suggest decreased levels of NET mRNA may contribute to cardiac sympathetic dysfunction in heart failure due to longterm VOL, which may lead to decreased myocardial β 1-AR mRNA. We conclude that the normal NET mRNA expression may play a critical role to maintain sensitivity of β 1-AR to adrenergic stimuli and cardiac contractility.

关 键 词：去甲肾上腺素 肾上腺素能 基因表达 心力衰竭 交感神经 心脏功能 转运蛋白 

分 类 号：R335.4[医药卫生—人体生理学] R541.6[医药卫生—基础医学]