Effect of desipramine on apoptosis and endoplasmic reticulum stress in atherosclerotic plaque of rabbits / 中国药理学通报

ABSTRACT

Aim: To investigate the effect of desipramine (DES) on apoptosis and endoplasmic reticulum stress(ERS) in atherosclerotic model of rabbits. Methods: The rabbit model of atherosclerosis (AS) was established through abdominal aorta balloon injury and high fat diets for 12 weeks. They were divided into high-fat diet(HFD) group and HFD + DES group randomly. The same numbers of healthy rabbits with chow diet were divided randomly into normal control (NC) group and DES group. All interventions were given for the last 4 weeks. At the end of week 12, serum lipid was tested by conventional method. Plasma ox-LDL was measured by ELISA. Plasma and arterial acid sphingomyelinase(ASM) activity and ceramide levels were detected by UPLC analysis. Cell apoptosis in abdominal aorta was measured by TUNEL staining. Expression of GRP78 and CHOP proteins were detected by Western blot. Results: On the one hand, DES had no effect on serum lipid profiles including TG, TC, HDL-C.LDL-C and ox-LDL levels compared with either healthy or atherosclerosis rabbits. On the other hand, DES inhibited ASM and ceramide levels both in plasma and aorta, and decreased apoptotic cells and proteins of GRP78 and CHOP expression in abdominal aorta. Conclusions: DES attenuates AS via inhibition of ASM, down-regulating ceramide, attenuating ERS and thus reducing the apoptosis of AS plaques.