A large number of studies have shown that oxidative

A large number of studies have shown that oxidative stress is involved in the pathophysiological process of ventricular remodeling and is associated with left ventricular dysfunction (Hori and Nishida, 2009, Lord et al., 2010). The generation of reactive oxygen species (ROS) that exceeds anti-oxidation capability will lead to the accumulation of reactive oxygen species (Falcão-Pires et al., 2011). Excessive reactive oxygen species could then disturb cell function, cause lipid peroxidation and DNA mutations and may result in irreversible cell damage or apoptosis (Murdoch et al., 2006, Sawyer et al., 2002). Apoptosis is also thought to be an important process that contributes to cardiac compensatory hypertrophy, which leads to heart failure (Bing, 1994). Herba Epimedii, a Chinese herbal medicine, has been widely used in the treatment of cardiovascular diseases (such as hypertension, ischemic cardiomyopathy, etc.), Alzheimer's disease, osteoporosis and immune function regulation (Sze et al., 2010, Tian et al., 2015). The flavonoids compound IcarisideII (IRSII) having a slight inhibitory effect on PDE5, is the main active components of epimedium in vivo. It has a wide range of pharmacological effects on oxidation and apoptosis (Gao et al., 2017, Khan et al., 2015). It has been reported that IcarisideII can inhibit H2O2 induced cell death in PC12 gtpase inhibitor (Gao et al., 2017). However, the protective effect of IcarisideII on left ventricular remodeling and its potential mechanism remain unknown. Spontaneously hypertensive rats (SHR) are an animal model for the study of left ventricular remodeling that results from long-term pressure overload (Damatto et al., 2016). Blood pressure in SHRs changes with increasing age, and hypertension is established at 3–4 months after birth. Hypertension increases to the highest level at 6 month, and rising blood pressure can cause ventricular remodeling (Zhang et al., 2014).
Materials and methods
Results
Discussion Hypertension is a major risk factor for cardiovascular events and approximately a third of hypertensive patients present with left ventricular remodeling (Materson, 2005). Left ventricular hypertrophy is a type of adaptive response to hypertension and it can maintain normal pump function with changes in cardiac structure and function. Early cardiac hypertrophy includes the enlargement of myocardial cells, which can reduce ventricular wall tension and maintain heart function (Frey and Olson, 2003). If the load continues to increase, heart remodeling and cardiac function disorder can develop (Gupta et al., 2014). In the previous experiments of our group, we tested IcarisideII doses of 3 and 10mg/kg in streptozotocin-induced cognitive deficits model (Yin et al., 2016). In published data (Wang et al., 2015, Tian et al., 2015), dose of 5mg/kg was used to improve erectile dysfunction and diabetic nephropathy. Regarding the minimum dosage, we take 4mg/kg which is the average values of 3 and 5mg/kg. Then we set 8 and 16mg/kg as the media and high dosages. In the preliminary experiment, 4mg/kg was administered with slight effect tend on reducing blood pressure and improving left ventricular function, while 8mg/kg and 16mg/kg was more effective. Hence three doses of 4mg/kg, 8mg/kg and 16mg/kg were decided in the present study to explore its effect on improving left ventricular remodeling and its mechanism. From 6 to 8 weeks, SHRs are in the of pre-hypertension stage- arterial hypertension starts to increase and provokes left ventricular hypertrophy. As the disease progress, many characteristics of hypertension that result in end target organ damage appear, such as ventricular hypertrophy, heart failure, etc. (Abbate et al., 2006). Therefore, SHRs are the ideal animal model for studying primary hypertension and its pathogenesis. In this study, we evaluated 26-week-old rats and found that the blood pressure of SHRs increased with age. The systolic pressure was 1.77 times higher than in WKY rats, and the diastolic pressure was 1.56 times higher (Fig. 1). From H&E staining, it can be observed that the myocardial cells were hypertrophied and disordered (Fig. 4). Additionally, Masson trichrome staining demonstrated significant interstitial collagen deposition (Fig. 5). Left ventricular diameter, wall thickness, ejection fraction and short axis shortening rate, which were measured by echocardiography, showed that 26-week old SHRs had worse left heart function (Fig. 2). The above results suggested that arterial hypertension and stable left ventricular hypertrophy had developed in 26-week-old SHRs. After IcarisideII intervention, the above mentioned pathological changes and heart function were improved to different extents. Therefore, we speculate that IcarisideII can improve SHR ventricular remodeling.