心康冲剂对慢性心力衰竭大鼠去甲肾上腺素转运蛋白及交感神经系统的影响

Effects of Xinkang Granule on norepinephrine transporter and sympathetic nervous system in rats with chronic heart failure

目的探讨心康冲剂对慢性心力衰竭大鼠去甲肾上腺素转运蛋白(norepinephrine transporter,NET)及交感神经系统表达的调控作用。方法经腹腔注射盐酸多柔比星建立慢性心力衰竭大鼠模型,造模成功后随机分为模型组、心康冲剂组、美托洛尔组,每组13只。另取10只大鼠为空白组。美托洛尔组予以酒石酸美托洛尔2.25 mg/kg,心康冲剂组予以心康冲剂1.08 g/kg,空白组与模型组予以生理盐水15 mL/kg。各组每天均灌胃1次,连续6周。实验结束后,心脏超声检测心功能;ELISA法检测血清脑钠肽(brain natriuretic peptide,BNP)、去甲肾上腺素(norepinephrine,NE)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)表达;HE染色检测心肌病理改变;RT-PCR检测心肌组织NET、TNF-αmRNA表达;Western blot检测NET表达;生物信号采集系统检测颈交感神经放电(sympathetic nervous system activity,SNA)情况。结果与空白组比较,模型组左室舒张期内径(left ventricular end diastolic internal dimension,LVIDd)、左室收缩末期内径(left ventricular end systolic internal dimension,LVIDs)、SNA、BNP、NE、TNF-α、TNF-αmRNA表达均明显升高(P<0.01),左室短轴缩短率(left ventricular fractional shortening,LVFS)、左室射血分数(left ventricular ejection fraction,LVEF)、NET、NET mRNA表达均明显降低(P<0.01)。与模型组比较,心康冲剂组和美托洛尔组LVEF、LVFS、NET、NET mRNA表达均明显升高(P<0.05),LVIDd、LVIDs、SNA、BNP、NE、TNF-α、TNF-αmRNA表达均明显降低(P<0.05)。与美托洛尔组比较,心康冲剂组NET mRNA表达明显升高(P<0.01),TNF-αmRNA表达明显降低(P<0.01)。心康冲剂组与美托洛尔组间LVEF、LVFS、LVIDd、LVIDs、SNA、BNP、NE、TNF-α、NET表达比较,差异均无统计学意义(P>0.05)。结论心康冲剂可改善慢性心力衰竭大鼠心功能,拮抗心室重塑,其机制可能与增加NET表达,下调心脏交感神经兴奋性有关。

Objective To explore the effects of Xinkang Granule(XKG)on the expression levels of norepinephrine transporter(NET)and sympathetic nervous system in rats with chronic heart failure(CHF).Methods The rat model of chronic heart failure was established by intraperitoneal injection of doxorubicin hydrochloride.After modeling,the rats were randomly divided into model group,XKG group and metoprolol group,with 13 rats in each group.Another 10 rats were selected as blank group.Metoprolol group was given metoprolol 2.25 mg/kg,XKG group was given Xinkang granule 1.08 g/kg,blank group and model group were given normal saline 15 mL/kg.Each group received intragastric administration once a day for 6 consecutive weeks.At the end of the experiment,cardiac function of rats in each group was detected by echocardiography.The levels of brain natriuretic peptide(BNP),norepinephrine(NE),and tumor necrosis factor-α(TNF-α)were detected by ELISA;cardiac muscles were detected by HE staining;RT-PCR was applied to detect the expression of NET and TNF-αmRNA;Western blot was used to detect the expression of NET.The discharge of cervical sympathetic nervous system activity was detected by biological signal acquisition system.Results Compared with blank group,the expressions of left ventricular end diastolic internal dimension(LVIDs),left ventricular end systolic internal dimension(LVIDd),SNA,BNP,NE,TNF-αand TNF-αmRNA in the model group were significantly higher(P<0.01),while the expression levels of left ventricular fractional shortening(LVFS),left ventricular ejection fraction(LVEF),NET and NET mRNA significantly decreased in the model group(P<0.01).Compared with the model group,the expression levels of LVEF,LVFS,NET and NET mRNA in XKG group and metoprolol group were significantly higher(P<0.05),while the expression levels of LVIDd,LVIDs,SNA,BNP,NE,TNF-αand TNF-αmRNA were significantly lower in XKG group and metoprolol group(P<0.05).Compared with metoprolol group,the expression of NET mRNA significantly increased and the expression of TNF-αmRNA significantly decreased in XKG group(P<0.01).There were no significant differences in LVEF,LVFS,LVIDd,LVIDs,SNA,BNP,NE,TNF-αand NET between XKG group and metoprolol group(P>0.05).Conclusion XKG can improve the cardiac function and antagonize ventricular remodeling in CHF rats.The mechanism may be related to the increase of NET expression and the down-regulation of cardiac sympathetic nerve excitation.