心康片对阿霉素诱导的心衰大鼠心肌细胞凋亡率、胶原容积分数、肌浆网Ca~(2+)-ATP酶活性的影响

【目的】探讨心康片对阿霉素诱导的慢性心力衰竭(简称心衰)大鼠心肌细胞凋亡率、胶原容积分数、肌浆网Ca2+-ATP酶活性的影响。【方法】采用SD大鼠腹腔内注射阿霉素法复制心衰大鼠模型。于造模成功后,随机分为5组:模型组,西药组,中药低、中、高剂量组,每组10只,分别给予蒸馏水,地高辛混悬液(22.5μg/kg),心康片水溶液(9、18、36 g/kg),将以上各药物应用蒸馏水稀释成等体积10 m L/kg灌胃,每日1次,连续给药5周。另随机选取同批次大鼠10只进入假手术组,腹腔内注射等量生理盐水,蒸馏水灌胃。通过TUNEL法检测大鼠心肌细胞凋亡率、Masson三色染色后计算大鼠心肌胶原容积分数(CVF)、定磷法测定肌浆网Ca2+-ATP酶(SERCA2a)活性。【结果】与假手术组比较,模型组心肌细胞凋亡率、CVF均显著升高(P0.01),提示心衰大鼠发生了病理性心肌重构;与模型组比较,西药组与中药低、中、高剂量组心肌细胞凋亡率显著下降(P0.01),提示地高辛与心康片均能一定程度上减少细胞凋亡。西药组与中剂量、高剂量中药组的心肌胶原容积分数均低于模型组(P0.05或P0.01),可见地高辛与心康片均可显著延缓心肌细胞的纤维化。同时,中药中、高剂量组心肌细胞SERCA2a活性均显著高于模型组(P0.05或P0.01),提示心康片可能通过调节SERCA2a活性的途径,从而减轻心肌重构,改善心脏功能。【结论】心康片可能通过调节SERCA2a活性降低心肌细胞凋亡率和心肌细胞容积分数,具有抗心肌细胞凋亡、抗心肌纤维化的作用,从而延缓心肌间质重构。

Effect of Xinkang Tablets on Myocardial Apoptosis Index,Collagen Volume Fraction and Sarcoplasmic Reticulum Ca2+-ATPase Activity of Rats with Adriamycin-induced Heart Failure

Objective To explore the effect of Xinkang Tablets on myocardial apoptosis index,collagen volume fraction and sarcoplasmic reticulum Ca2+-ATPase activity of rats with adriamycin-induced heart failure.Methods The chronic heart failure (CHF) SD rat model was established by intraperitoneal injection of doxorubicin.After successful modeling,the rats with CHF were randomly divided into 5 groups,namely model group,western medicine group,and low-,middle-and high-dose of Chinese medicine groups,10 rats in each group.The rats in the above groups were given intragastric administration of distilled water,22.5 μg/kg of Digoxin mixed suspension,9,18,36 g/kg of XinkangTablets,respectively,in the volume of 10 mL/kg of distilled water dilution,once a day,for 5 continuous weeks.Another the same batch of 10 SD rats were randomly allocated to the sham operation group,and were treated with intragastric administration of the same volume of distilled water.And then the apoptotic rate of myocardial cells was measured by TUNEL method,the collagen volume fraction (CVF) was measured after Masson staining,and the sarcoplasmic reticulum Ca2+-ATPase activity was determined by inorganic phosphate assay.Results Compared with the sham operation group,the apoptotic rate of myocardial cells and CVF in the model group were increased(P ＜ 0.01),indicating that the myocardial remodeling occurred in rats with CHF.Compared with the model Group,the apoptotic rate of western medicine group and three Chinese medicine groups was significantly decreased(P ＜ 0.01),suggesting that Digoxin and Xinkang Tablets can relieve apoptosis to certain extent.The CVF in Digoxin group and middle-and high-dose of Chinese medicine groups were lower than those in the model Group (P＜ 0.05 or P＜ 0.01),indicating that Digoxin and Xinkang Tablets can delay the myocardial fibrosis.Last but not least,the SERCA2a activities in the middle-and high-dose of Chinese medicine groups were higher than those in the model group (P ＜ 0.05 or P ＜ 0.01),suggesting that Xinkang Tablets may relieve myocardial remodeling and improve cardiac function through the regulation of SERCA2a activity.Conclusion Xinkang Tablets decrease the apoptotic rate and myocardial cell volume fraction probably through the regulation of SERCA2a activity,which may play a role in counteracting apoptosis and myocardial fibrosis,and ultimately delay the remodeling of the myocardium.