Icariside II improves left ventricular function by improving endoplasmic reticulum stress and caspase 12 signaling in SHR / 中国药理学通报

ABSTRACT

Aim: To explore the mechanism of icariside II (ICS II) on improving left ventricular function based on endoplasmic reticulum stress and caspase-12 signaling in spontaneously hypertensive rats (SHRs). Methods: Thirty 14-week-old male SHRs were divided into model group, ICS II low, middle and high dose groups and positive drug group (n = 6). WKY was used as control group (n =6). ICS II groups were respectively given ICS 114, 8, 16 mg · kg-1(ig, qd), and positive drug group was given losartan (20 mg · kg-1). At the end of 26th weeks, anesthetized rats were measured by ultrasound for detection of the left ventricular function, RT-PCR was used to determine the level of GRP78 mR- NA in the left ventricle tissue, and Western blot was used to assess the levels of GRP78 and cleaved-caspase- 12/9/3 protein in the left ventricle tissues. Results: Compared with WKY group, the internal diameter and posterior wall thickness of the left ventricular end diastolic increased, while the ejection fraction and fractional shortening decreased in SHR group. GRP78 mRNA and protein levels were up-regulated, and the levels of cleaved-caspase-12/9/3 protein were raised in left ventricle (P < 0.05). Compared with SHR group, the internal diameter and posterior wall thickness of the left ventricular end diastolic increased in ICS II medium and high dose groups and positive drug group (P <0. 05), while the ejection fraction and fractional shortening decreased (P<0.05). GRP78 mRNA and protein levels were down-regulated, the levels of cleaved-caspase-12/ 9/3 protein declined in left ventricle (P <0.05). Conclusions: ICS II could improve left ventricular function in SHRs, and its mechanism may be related to improving left ventricular endoplasmic reticulum stress and down-regulating the elevated caspase-12 signaling.