葶苈子抗心衰有效组分筛选及其作用机制分析

Effective Fractions and Mechanism of Descurainiae Semen Lepidii Semen in Chronic Heart Failure Rats

摘要:

目的：筛选葶苈子抗心衰的有效组分，并对其机制进行初步探讨。方法：雄性SD大鼠随机分为正常组，模型组，阳性药物组（地高辛组）和葶苈子不同剂量组，除正常组外采用腹腔注射阿霉素6周复制心衰大鼠模型，药物灌胃干预4周，大鼠代谢笼法收集6 h尿液，超声心动图检测心功能变化。处死后称取每组大鼠的体重和心脏质量，计算心脏系数。采用酶联免疫吸附试验（ELISA）测定血清脑钠肽（BNP），肌钙蛋白I（cTnI），血浆血管紧张素II（AngⅡ），醛固酮（ALD）水平，心肌超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量。采用二硫代二硝基苯甲酸法测定心肌谷胱甘肽过氧化物酶（GSH-Px）活力，并运用光镜观察心肌组织病理形态学改变。结果：与正常组比较，模型组大鼠BNP，cTnI，AngⅡ，ALD水平明显升高，心衰大鼠的左室射血分数（LVEF）和左室短轴缩短率（LVFS）显著降低，心肌组织MDA含量显著升高和SOD，GSH-Px活性显著降低，尿量明显降低（P<0.05，P<0.01），心肌病理损伤较为明显；与模型组比较，葶苈子发挥抗心衰作用的有效组分为水部位，可以显著降低BNP，cTnI，AngⅡ，ALD水平（P<0.05，P<0.01），升高心衰大鼠的LVEF和LVFS（P<0.05，P<0.01），并能减轻心肌病理损伤；且葶苈子中、高剂量组可以极显著降低心肌组织MDA含量和升高SOD活性（P<0.01），具有较好的利尿作用（P<0.05），同时中剂量组使GSH-Px活力显著增高（P<0.05）。结论：葶苈子有效组分水部位能够显著改善心衰症状，其作用机制可能与改善心衰大鼠体内氧化应激失衡状态，抑制神经内分泌系统过度激活密切相关。

Abstract:

Objective: To screen the effective parts of Descurainiae Semen Lepidii Semen(DSLS) that play a role in anti-heart failure and explore its mechanism. Method: The male sprague dawley (SD) rats were randomly divided into normal group, model group, positive drug group (digoxin group), DSLS low dose, middle dose and high dose groups. The chronic heart failure (CHF) models were established by intraperitoneal injection of doxorubicin for 6 weeks. The drugs were given for 4 weeks by intragastric administration; metabolic cage method was used to collect 6 h urine, and cardiac function changes were measured by ultrasonic echocardiogram. Body weight and heart weight of the rats were measured in each group to calculate the cardiac index after the rats were sacrificed. The levels of brain natriuretic peptide(BNP), cardiactroponin I (cTnI), angiotensin Ⅱ (AngⅡ), and aldosterone (ALD) in blood, as well as the activities of superoxidedismutase (SOD) and methane picarboxylic aldehyde (MDA) contents were measured by ELISA. The activities of glutathione peroxidase (GSH-Px) in myocardial tissues were evaluated by using dithio-bis-nitrobenzoic acid (DTNB) method. Histopathological changes of myocardium were visualized under light microscope. Result: As compared with normal group, the levels of BNP, cTnI, AngⅡ and ALD were significantly higher in model group; left ventricular ejection function (LVEF) and left ventricular fractional shortening rate (LVFS) in model rats were significantly reduced; MDA content was significantly increased; SOD and GSH-Px activities were significantly reduced; urine volume was significantly reduced (P<0.05, P<0.01); with more obvious myocardial pathological injury. As compared with the model group, the effective fractions of DSLS significantly reduced the levels of BNP, cTnI, AngⅡ, and ALD (P<0.05, P<0.01), increased LVEF and LVFS (P<0.05, P<0.01), and reduced myocardial pathological damage in heart failure rats. Moreover, the high-dose and middle-dose DSLS groups significantly reduced content of MDA, and increased activity of SOD (P<0.01), with a good diuretic effect (P<0.05). Meanwhile, middle-dose group could significantly improve the activity of GSH-Px (P<0.05). Conclusion: The water extracts from effective fractions of DSLS could significantly improve the heart failure symptoms in rats. Its mechanism may be associated with improving the unbalance of oxidative stress in vivo and inhibiting the excessive activation of neuroendocrine in CHF rats.