关键词: Wistar大鼠；曲妥珠；心脏毒性；心脏超声；凋亡

Abstract:

Objective   To observe the effect of trastuzumab on cardiac function of rats and to investigate the possible mechanisms. Methods   A total of 20 Wistar rats were randomly divided into the experimental and control group, with 10 in each. Rats in the experimental group received daily intraperitoneal injection of trastuzumab (12mg/kg in the first day and then 6 mg/kg in the following 6 days). The cumulative dose of trastuzumab was 48mg/kg. Rats in the control group were given the same volume of saline. The cardiac function was evaluated with echocardiogram before and after trastuzumab administration. Myocardial cell apoptosis was determined with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Apoptotic index was calculated with reference to the results of TUNEL staining. The activity of Caspsase-3 was measured with colorimetic assay. Results   Compared with the control group, in the experimental group, the left ventricular end systolic diameter (LVED) significantly increased; the left ventricle posterior wall (LVPW) became thinner; the left ventricular ejection fraction (LVEF) reduced; the left ventricular fractional shortening (LVFS) declined(P＜0.01); the number of apoptotic myocardial cells and activity of Caspase-3 were both significantly higher (P<0.001). The degree of myocardial cell apoptosis was positively associated with left ventricular diameter and negatively correlated with left ventricular wall thickness. Conclusion    Consecutive multiple intraperitoneal injections of trastuzumab could impair cardiac function in rats, which may be associated with the apoptosis of myocardial cells.

Key words: Wistar rats; Trastuzumab; Cardiotoxicity; Echocardiogram; Apoptosis