大鼠压力负荷性肥大心肌中TNF-αmRNA表达变化

Expression of TNF-α mRNA in hypertrophic myocardium by pressure overload in rats

目的 :探讨大鼠压力负荷性肥大心肌中TNF -αmRNA表达的变化及卡托普利 (captopril)对其的影响。方法 :采用腹主动脉缩窄法复制压力超负荷心肌肥大模型 ,于术后 4 2d采血、摘取心脏 ,测定心肌肥大指数并采用酶联免疫法测定血清及左心室肌TNF -α含量 ;应用心肌原位杂交法结合图像分析系统检测心肌组织中TNF -αmRNA表达的变化 ,并观测TNF -αmRNA在心肌组织中的定位。结果 :术后 4 2d心肌明显肥大 ,以左心室为主 ;主动脉缩窄 (aorta -constriction ,AC)组心室肌TNF -α含量比假手术 (sham -operation ,SO)组高 98% (P <0 0 1) ;卡托普利干预使心室肌TNF -α含量比AC组低 6 4 14 % (P <0 0 1) ,但未达到对照水平 ;心肌组织原位杂交显示TNF -αmRNA表达主要在心肌间质部位 ,假手术组心肌TNF -αmRNA表达水平极低 ,明显低于AC术后 (P <0 0 1) ,captopril干预虽明显抑制AC术后心肌组织中TNF -αmRNA表达 ,但并未使其达到SO组水平。结论 :心肌组织内源性TNF -α的表达增加在压力负荷性心肌肥大中具有重要的调控作用 ,其过表达可能与RAS激活促心肌间质TNF

AIM: To observe the change of TNF-α mRNA in hypertrophic cardiac myocytes induced by pressure overload in rats and the effect of captopril. METHODS: Serum and heart were collected 42 days after the cardiac hypertrophy model made by pressure overload by abdomen aorta-constriction (AC). Hypertrophic parameter and the concentration of TNF-α in serum and left ventricle were determined by ELISA. TNF-α mRNA in cardiac myocytes was determined by in situ hybridization and analyze by ELIA image analysis system. The orientation of (TNF-α) mRNA in cardiac myocytes was also observed. RESULTS: Left ventricle hypertrophy was observed 42 days after operation. TNF-α mRNA in AC group elevated 98% compared to sham-operated group and descended 64.14% by captopril ((P<0.01),) but did not descend to the normal level. The expression of TNF-α mRNA showed mostly in myocardial matrix by in situ hybridization. The level of expression was very low in sham-operation group and markedly enhanced after aorta-constriction, but it was decreased when treated by captopril. CONCLUSION: Endogenous TNF-α acts as an important adjustive factor in the pressure overload-induced cardiac hypertrophy and TNF-α mRNA increased in myocardial matrix may be activated by renin-angiotension system.