| ObjectivesAortic valve stenosis is a common clinical disease leading to left ventricular pressure overload. Myocardial remodeling, such as myocardial hypertrophy, interstitial fibrosis, microvascular structure sabotage and other pathological changes, happens under the stimuli of the mechanical stress increases, internal environment changes and so on at the condition of left ventricular pressure overloading. Myocardial hypertrophy is an important aspect of myocardial remodeling. Aortic valve replacement surgery is a typical process of left ventricular unloading. However, aortic valve replacement surgery does not make all patients benefit equally. It can not effectively restore heart function to those patients who suffer a long duration of chronic aortic valve stenosis.Mangiferin has a wide range of pharmacological activity to the central nervous system, respiratory system. In addition, it also has the effects of anti-radiation, antineoplastic, anti-diabetic, anti-inflammatory and immune regulation. More and more research emerge to its effects of cardiovascular system at recent years. In this study, we will combine the animal models of left ventricular pressure overloading/unloading with the mangiferin intervene to investigate the reversal effect of the pressure unloading and mangiferin to the left ventricular hypertrophy. It could provide a theoretical basis whether to continue the treatment of myocardial hypertrophy after the aortic valve replacement surgery in clinical practice.Methods1. Build the pressure overload/unload model: we exposed the ascending aorta from the path of the upper corner of the sternum, playing a slipknot after 4-0Prolene plastic string encircles the ascending aorta, the diameter of 1.4mm steel wire was placed inside the knot running parallel to the ascending aorta and tightened up. It produced aortic stenosis after withdrawing the wire immediately. We released the pressure overloading with the same surgical path by cutting the ligature.2. Animal groups: wild type SD rats were chosen for the study and divided into five groups randomly. Sham group: SD rats underwent sham surgery, which was exposed the ascending aorta and closed the thoracic cavity; Overload group: SD rats underwent the ascending aortic coarctation surgery and survived six weeks; Unloading Group: relieve the aortic coarctation after undergoing it 6 weeks, 2ml vegetable oil gavage(1/day for 4 weeks); Mangiferin Group: relieve the aortic coarctation after undergoing it 6 weeks, mangiferin(20mg/kg) dissolved in 2ml vegetable oil gavage(1/day for 4 weeks).3. Cardiac echocardiography: when aortic coarctation six weeks and release it four weeks, detecting the echocardiography data of systolic interventricular septal thickness(IVSs), systolic left ventricular posterior wall thickness(LVPWs), left ventricular end-systolic inside diameter(LVIDs) diastolic interventricular septal thickness(IVSd), diastolic left ventricular posterior wall thickness(LVPWd), left ventricular end-diastolic diameter(LVIDd).4. Heart mass: weighing body weight(BW) and heart weight(HW) when the observation time arrived, calculate the ratio of heart weight and body mass weight(HW / BW).5. Histopathological observation: The removed heart by 36 h formaldehyde solution fixed and paraffin-embedded sections were used for Masson staining and hematoxylineosin(HE) staining, microscopy image acquisition system with myocardial pathological changes and save the images.Results1. The mortality rate of aortic coarctation surgery is 16.7%; that of relieve surgery is 20.0%; at last 10 rats in sham group, 12 rats in the control group, 10 rats in overload group, group and every 8 rats in unloading and mangiferin group.2. Compared with the sham group, the thickness of LVPWs(4.25 ± 0.43mm), LVPWd(2.89 ± 0.42mm), IVSs(3.92 ± 0.71mm), IVSd(2.59 ± 0.49 mm) in overload myocardial group was significantly thicker(P <0.01). The heart volume and cardiac mass body weight ratio(4.44 ± 0.77 mg / g) were significantly increased(P <0.01); Besides, disordered arrangement of myocardial cells appeared, cytoplasm of myocardial cells increased and interstitial fibrosis was obvious. Therefore, SD rat ventricular hypertrophy model was constructed successfully.3. Compared with the overload group, the thickness of LVPWs(3.85 ± 0.56mm), LVPWd(2.47 ± 0.52mm), IVSs(3.81 ± 0.53mm), IVSd(2.51 ± 0.54mm) in unloading myocardial group improved to some extent, but not obvious. Besides, the heart volume and heart mass body weight ratio(3.03 ± 0.18 mg / g) decreased. In the meantime, myocardial cells shrinkaged but disorganized, and there was no significant reduction in interstitial fibrosis.4. After unloading with Mangiferin, the thickness of LVPWs(2.80±0.37 mm), LVPWd(1.94±0.27mm), IVSs(2.90±0.51mm), IVSd(1.89±0.38mm) and heart mass body weight ratio(2.32±0.33 mg/g)improved significantly(P <0.01). In addition, myocardial cell shrinkaged and arranged regularly, and interstitial fibrosis improved to some extent.Conclusion 1. SD rat model of left ventricular hypertrophy can be successfully established with Aortic coarctation-induced left ventricular pressure overloading in six weeks. This surgery method avoids rat tracheal intubation, and the narrow place was closed to the aortic valve. So, it simulated the pathophysiological processes of clinical aortic stenosis effectively.2. After left ventricular unloading in four weeks, left ventricular hypertrophy of SD rat improved to some extent, but not completely. Unloading combined with Mangiferin had more significant effect than single unloading in reversing left ventricular hypertrophy of SD rats.3. The left interior diameter of groups of rats showed no difference in statistical, the reason may be that cardiac function was still in the stage of compensation after left ventricular overloading with six weeks. So there was no decompensated performance such as increased left interior diameter, cardiac wall thinning and so on. |
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