不同心脏负荷及心室内压变化对大鼠早期心肌原癌基因表达的影响  

Immediate-early gene responses to different cardiac loads and ventricular pressure in the rat left ventricle

作　　者：李贺[1] 李锦毅[2] 胡小萍[3] 白旭芳[3] 费俭[3] 

机构地区：[1]武警医学院附属医院心内科 [2]中国医科大学肿瘤研究所第四研究室,辽宁沈阳110001 [3]中科院上海生物化学与细胞生物学研究所神经分子生物学实验室

出　　处：《中国医科大学学报》2004年第6期490-492,共3页Journal of China Medical University

基　　金：国家自然科学基金资助项目(39470838)

摘　　要：目的检测容量(VOL)和压力超负荷(POL)早期大鼠左心室内压变化诱导左心室心肌原癌基因cfos、cjun、cmyc、egr1mRNA表达时间变化和差异。方法测定假手术大鼠、及心脏超负荷后不同时间点左心室收缩压(LVSP)和内压谷值(LVDP)变化,用狭缝杂交检测各时间点左室心肌cfos、cjun、cmyc、egr1mRNA表达,用密度仪定量分析。结果与假手术组比较,不同心脏负荷后早期LVSP均下降(P<0.05),48hVOL组最低,POL组恢复至对照组水平;负荷后LVDP逐渐增高,POL后6h,VOL12h最高(P<0.05),后者48h与假手术组相近(P>0.05)。POL诱导原癌基因表达峰值早于VOL,48hcmyc、cjun出现第2次表达增加。VOL后1h检测到cfos、cjun、egr1、cmyc弱表达,48hcfos无表达,cjun表达减弱,cmyc和egr1仍有较高表达。结论VOL、POL后左室内压增加诱导不同的心肌cfos、cjun、cmyc、egr1表达增加的时间顺序,与LVDP增高无关,cfos、cjun、cmyc表达与LVSP增高有关,提示左心室主动收缩产生的室内压为诱导原癌基因表达的主要因素;心脏超负荷后心肌原癌基因可持续表达,不同负荷原癌基因表达的时间过程差异可能对发生不同类型心肌肥厚有重要影响。Objective: To investigate the effect of intraventricularpressure change by volume (VOL) and pressure overload (POL) on expressions of proto-oncogene c-fos,c-jun,c-myc, and egr-1 in vivo.Methods: Left ventricular systolic pressure (LVSP) and left ventricular diastolic pressure (LVDP) and the mRNAs of the genes of rats with VOL and POL induced by aortacaval fistula and abdominal aortic constriction operation and control group were measured at different time points after the operation. Results:Be compared with the control group,LVSP of both groupos decreased (P<0.05) and 48h later hour VOL group declined most remarkably, POL group recovered to the control level.LVDP gradually increased after the imposition of both acute overload, reached peak 12 hour later (P<0.05), and declined thereafter. The peak value of mRNAs expression of the genes induced by POL were earlier than VOL group.In POL group c-jun and c-myc increased again 48 hour after operation. In VOL rats,c-fos,c-jun egr-1,and c-myc mRNA signals appeared at 1-hour point. At 48 hour point the c-fos mRNA were not detected, c-jun showed weak expression,c-myc and egr-1 were still in higher level. Conclusion: These sequential changes of the proto-oncogenes expression may reflect the time course regularity of the proto-oncogenes expression induced by VOL and POL overload. During early phase of the overloads, the groups expression levels do not strengthen with the increase of LVDP,c-fos,c-jun and c-myc expression levels are related with LVSP increase,which indicate the protooncogenes expression initiates while heart load accumulates to some extent and duration and after that the load magnitude may not play a critical role for the expressions, and ventricular pressure generated by active ventricle contraction may play an important role in the proto-oncogenes expression.

关 键 词：心脏超负荷模型 大鼠 心室内压 原癌基因表达 

分 类 号：R730.2[医药卫生—肿瘤]