葛根素对慢性心肌纤维化大鼠心脏功能和结缔组织生长因子的影响

Effects of Puerarin on cardiac function and connective tissue growth factor in myocardiac tissue of rat with chronic myocardial fibrosis

目的研究葛根素对慢性心肌纤维化大鼠的心脏功能和心肌结缔组织生长因子(connective tissue growth factor,CTGF)的影响。方法采用异丙肾上腺素(isoprenaline,ISO)5mg/kg·d×10d皮下注射制作大鼠慢性心肌纤维化模型,分早期和后期给予葛根素(100mg/kg·d)腹腔注射分别56d和46d。对48只雄性SD大鼠进行随机分组:造模组(M组)16只;对照组(C组)8只;早期干预组(Pa组)12只;后期治疗组(Pp组)12只。实验8周末对大鼠进行超声心动图检测左室射血分数(left ventricle ejection frac-tion,LVEF)及缩短分数(fractional shortening,FS),计算左心指数,进行VG(VanGieson)染色测算胶原容积积分(collagen volume fraction,CVF),RT-PCR检测CTGF mRNA水平。结果Pa组和Pp组的左心指数、CVF和CTGF均较M组明显减少(P<0.01),LVEF和FS则较M组明显增加(P<0.01);Pa组的左心指数和CTGF较Pp组明显减少(P<0.05),而CVF减少更为显著(P<0.01);Pa组的LVEF、FS则明显增加(P<0.01),其中Pa组的LVEF与C组无显著差异(P=0.075)。结论葛根素可抑制ISO诱导的心肌CTGF过表达,减少胶原沉积,从而改善心脏功能。

Objective To investigate the effects of Puerarin on cardiac function and connective tissue growth factor （CTGF） in myocardiac tissue of rat with chronic myocardial fibrosis.Methods In this study,rat model of chronic myocardial fibrosis was established by subcutaneous injection （s.c.） with ISO （0.05% ISO, 5 mg/kg per day for ten days）.Meanwhile,rats were administrated by intraperitoneal injection（i.p.）with peurarin （100mg/kg per dayfor 56 or 46 days）.The period of the present study of animals was 8 weeks.48 Sprague-Dawley male rats weighting 150 to 170 g were derided into four groups randomly：model group （M group, n=16）, control group （C group,n= 8）, early treatment by puerarin group （Pa group,n=12）,later treatment by puerarin group （Pp group, n=12）. At the end of study, left ventricle ejection fraction （LVEF） and fractional shortening （FS） were detected with ultrasound cardiography. Then left ventricle （LV） weight to body weight ratio was assessed.The cross serial sections of LV of the rats were examinated microscopically after Van Gieson （VG） collagen stained. The quantitative analyses of collagen volume fraction （CVF） was performed using an image analyser computer system.CTGF mRNA level in myocardiac tissue were measured.Results There were 8 survival rats in every group at the end of the present experiment.VG staining of M group showed a abundant of collogen in myocardial interstitium.Peurarin decreased the LV weight to body weight ratio, CVF and CTGF mRNA in myocardiac tissue induced by ISO in rats （P〈0.01）while it increased the LVEF and FS of rats （P〈0.01）.It was＇ no significant difference in LVEF between Pa group and C group. Conclusion These results show that peurarin decrease the excessive myocardial fibrosis induced by ISO in rat and improve cardial function of rats with chronic myocardial fibrosis mostly through suppressing the overexpression of CTGF in myocardial tissue.