摘要
目的:通过人工套接大鼠右侧颈动静脉,造成左向右分流,建立右心室容量、压力负荷增加的大鼠模型,观察右心室心肌细胞在此模型中的改变及其可能的临床意义。方法:设4个实验组与4个对照组,每组10只体重、性别相匹配的近交系Wistar大鼠。实验组无菌手术造成左向右分流,于术后1、2、4、8周分别将测量实验动物体重及右心室压力,并分别称取右心室(R)及左心室加室间隔(L+S)的质量,以及右心室与左心室加室间隔质量之比[R/(L+S)];右心室质量与体重之比(RV g/BW mg)。右心室组织切片,HE染色,应用相关软件分析右心室心肌细胞长宽比(μm/μm)、心肌细胞横断面积(μm2)的改变;应用RT-PCR法测定心肌细胞β肌球蛋白重链、心肌细胞表面β肾上腺素受体(-βAR)以及心肌细胞bcl-2基因mRNA表达量的改变。对照组大鼠手术操作同实验组,唯不套接颈动静脉,同样条件饲养。结果:术后第1周开始,实验组大鼠右心室压力即明显高于对照组,并且维持在一个相对稳定的高水平上。术后第1、24、8、周之间相比,无统计学意义。所有实验大鼠均未发生心衰现象;与对照组相比:①实验组大鼠(RV mg/BW g)在术后8周时结果为(0.64±0.05 vs 0.43±0.03,P<0.01);R/(L+S)至第8周时,结果为(0.36±0.04 vs 0.21±0.02,P<0.05);②实验组大鼠右心室心肌细胞长宽比在术后4周时为[(7.1±0.3):1降低至(6.5±0.3):1,P<0.05],而心肌细胞横断面积由250.4μm2增至328.8μm2(P<0.05)。第8周时改变依然存在,但与第4周相比,差异无统计学意义(P>0.05);③β肌球蛋白重链基因表达量在术后第1周时为(1.37±0.21 vs 0.77±0.15,P<0.01);第2周时仍表达增加,但与术后第1周相比,差异无统计学意义(P>0.05)。第4、第8周时,该基因的表达量明显下降,与对照组相比,差异无统计学意义(P>0.05);④-βAR mRNA表达量在术后第1周即降低(0.47±0.13 vs 0.80±0.12,P<0.05),第2、4、8周时改变依然存在,但与第1周时相比,差异无统计学意义(P>0.05);⑤心肌细胞bcl-2基因表达量在术后第1、2周均增加(0.28±0.07 vs 0.16±0.03,0.27±0.07 vs 0.15±0.04,P均<0.01),第4、8周与对照组相比改变不明显。结论:①人工套接大鼠颈动静脉能够造成右心室容量压力负荷上升,且这种负荷改变能够引起大鼠右心室的重塑;②β肌球蛋白重链基因、β肾上腺素受体基因、心肌细胞bcl-2基因在早期即可发生明显改变,并呈动态变化,反映心肌细胞对环境改变的迅速适应;心肌细胞形态改变发生稍晚,是早期基因表达改变的后果。
Objective： To investigate the changes and clinical significance of myocyte in right ventricle myocardial remodeling, a special technique connecting the arteria carotis communnis and venae jugularis extema was developed, and an artificial shunt of left to right was made resulting in volume and pressure overload in rat models. Methods： There were four experimental groups and four control groups, and each had 10 weigh/sex matched Wistar rats. The experimental groups received the surgery mentioned above. After 1, 2, 4 and 8 weeks, the right ventricle pressure through the puncture of the right ventricle was measured directly. Histology and RT-PCR were used to examine the right ventricle remodeling and the changes of gene expression of β-myosin heavy chain, β-adrenergic receptors and bcl-2 in the right ventricle remodeling. Results： The right ventricle pressure elevated and maintained relatively stable at the 1st, 2nd, 4th and 8th week after surgery. No heart failure occurred in all groups. （ 1 ） There was increment of the ratio of right ventricle weight to the body weight（RV mg/BW g） after 4 weeks, and a statistical significance between the 8-week group and the control group （0.64 ±0.05 vs 0.43 ±0.03,P 〈0.01）; at the same time, the right ventricle/（left ventricle ＋ septum） [ R/（ L ± S ） ] ratio increased too （0.36 ±0.04 vs 0.21 ±0.02, P 〈 0.05 ） ; （2） at the 4th week, the ratio of myocyte length to myocyte width and the myocyte cross-sectional area changed obviously. The ratio of myocyte length to myocyte width decreased [ （ 7.1 ± 0.3） ： 1 vs （6.5 ± 0.3） ： 1, P 〈 0.05 ], meanwhile the myocyte cross-sectional area increased from 250.4 μm^2 to 328.8 μm^2 （ P 〈 0.05）. At the 8th week, the changes still existed, but there was no statistical significance between the 4th and the 8th week; （3） the changes of gene expression of β-myosin heavy chain increased at the 1st week（1.37 ±0.21 vs 0.77 ± 0.15, average of densitometry, P 〈0.01） and the 2nd week（1.39 ± 0.32 vs 0.79 ± 0.17, average of densitometry, P 〈0.01）, and there was no significance between the 1st and the 2nd week. At the 4th and the 8th week, it returned to normal level; （4） the changes of gene expression of β-adrenergie receptors decreased at the 1st week （0.47 ±0.13 vs 0.80±0.12,P 〈0.05, average of densitometry）. At the 2nd, 4th and 8th week, the changes still existed, but there was no difference among them and all of them had no difference from the 1st week; （5） the gene expression of bcl-2 elevated at the 1st and the 2nd week（the 1st week： 0.28±0.07 vs 0.16± 0.03,P 〈0.01; the 2nd week： 0.27 ±0.07 vs 0.15 ±0.04, P 〈0.01, average of densitometry）. No changes occurred in the later 4 weeks. There was no difference between the 4th and the 8th week. Conclusion： Right ventricle overload could be developed by connecting the arteria carotis communis and venae jngularis extema and induce myocardial remodeling. The gene expression of β-myosin heavy chain, β-adrenergie receptors and bcl-2 would be changed very soon according to the environraent, which would do benefit for the heart function. The histological changes occur later, which is the result of early gene expression.
出处
《山东大学学报（医学版）》
CAS
北大核心
2006年第12期1224-1228,1232,共6页
Journal of Shandong University:Health Sciences
