Icariin protects myocardial cells in spontaneously hypertensive rats by inhibiting mitochondrial and endopla smic reticulum stress related pathways

Abstract

Purpose: To investigate the protective effect of icariin (ICA) on myocardial cells in spontaneously hypertensive rats (SHRs), and the mechanism involved. Methods: Twenty-four SPF-grade, 12-week-old SHRs were randomly assigned to model group and ICA group, with 12 rats/group. There were 12 Wistar-Kyoto (WKY) rats (aged 12 weeks) in the control group. Rats in ICA group were given ICA suspension (40 mg/kg) through gavage, daily for 3 months, while model rats were given equivalent volume of double distilled water (in place of ICA suspension) via gavage for 12 weeks. Blood pressure, cardiac function, left ventricular (LV) mass index, myocardial morphology and apoptosis-related protein levels were determined and compared among the four groups. Results: The myocardial cells were hypertrophic and disorderly arranged, with widened intercellular spaces. Besides, there were increases in protein expression levels of p53, caspase 3, Bok, Bax, GRP78, p-PERK, ATF-4, CHOP and DR5, while Bcl-2 protein was down-regulated. In contrast, the levels of these indicators in the ICA group were significantly better than those in the model group (p < 0.05). Conclusion: ICA reduces blood pressure in rats, but improves cardiac function and cardiomyocyte morphology by decreasing apoptosis in cardiomyocytes through down-regulation of mitochondrial and endoplasmic reticulum (ER) stress-related apoptosis pathways. Thus, icariin may be suitable for the treatment of hypertension; however, clinical trials need to be undertaken first.