Protective Effect of Wenyang Huoxue Huatan Prescription on Cardiotoxicity Induced by Anthracyclines / 中国实验方剂学杂志

ABSTRACT

Objective:To study the protective effect of the Wenyang Huoxue Huatan prescription （WYHXHT） on cardiotoxicity induced by adriamycin. Method:SD rats were randomly divided into the following six groups： a normal control group， an adriamycin model group， a low-dose （4.86 g·kg^-1） WYHXHT group， a middle-dose （9.72 g·kg^-1） WYHXHT group， a high-dose （19.44 g·kg^-1） WYHXHT group， and a dexrazoxane group. Except for the normal control group， the rats in other groups received intraperitoneal injection of 2.5 mg·kg^-1 adriamycin， once a week for six weeks， with a cumulative dose of 15 mg·kg^-1. The normal control group， the adriamycin model group， and the dexrazoxane group received 10 mL·kg^-1 normal saline daily by gavage. In the dexrazoxane group， the rats were subjected to intraperitoneal injection of 25 mg·kg^-1 dexrazoxane 30 min before doxorubicin administration， once a week for six weeks. The general condition of rats was observed and their body weight was monitored. A high-resolution micro-ultrasound imaging system was used to detect rat cardiac function. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes of myocardial tissues of rats. Western blot was used to detect the protein expression of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， the mammalian homolog of yeast Atg6 （Beclin-1）， and p62 protein in rat myocardial tissues. Result:Compared with the normal control group， rats in the adriamycin model group showed dull fur， reduced food intake and activity， loose stool， low energy， and slow response. Besides， it also displayed reduced body weight （<italic>P</italic><0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （<italic>P</italic><0.01）， myocardial cell degeneration， edema， rupture， and dissolution， expansion of myocardial interstitium， uneven staining of myocardial fiber， visible inflammatory cell infiltration， up-regulated expression of Beclin-1 and LC3Ⅱ in rat myocardial tissues （<italic>P</italic><0.01）， and down-regulated p62 expression （<italic>P</italic><0.01）. Compared with the adriamycin model group， the medium- and high-dose WYHXHT groups exhibited increased body weight， LVEF， and LVFS （<italic>P</italic><0.01）， relieved pathological injury of myocardial tissues， down-regulated expression of LC3Ⅱ and Beclin-1 （<italic>P</italic><0.05，<italic>P</italic><0.01）， and up-regulated expression of p62 （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:WYHXHT can effectively prevent and treat adriamycin-induced cardiotoxicity， and its effect may be related to the inhibition of myocardial cell autophagy. The effect is dominant in the high-dose group.