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·基础医学论著/研究·

橙皮素对异丙基肾上腺素诱导大鼠心衰的保护作用

曹静1，吕吉元1，张明升2，师锐赞2，冯巧爱3

目的观察橙皮素对大剂量异丙基肾上腺素(ISO)诱导大鼠心衰的保护作用，并探讨其机制。方法将SD大鼠随机分为正常(C)组、橙皮素对照(H)组、异丙基肾上腺素(I)组和橙皮素治疗+I(T)组，I组和T组接受皮下注射大剂量ISO(150 mg/kg)，2周后行超声心动图检测。确定造模成功后，H组及T组给予橙皮素(100 mg/kg)灌胃，I组给予等量的溶剂乙醇，连续给药10 d后测定各组大鼠心脏功能包括左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(EF)、左室缩短分数(FS)变化及血清丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(TAOC)的变化，观察各组大鼠心肌的病理变化。结果与C组比较，I组LVEDD变化不大，LVESD值增大、EF、FS降低，氧化应激指标中MDA值升高，SOD、TAOC降低，各指标差异有统计学意义(P<0.05)；与I组比较，T组大鼠LVEDD无明显变化，LVESD降低，EF、FS升高，血清MDA值降低，SOD、TAOC升高，各指标差异有统计学意义(P<0.05)。H组各指标较C组无明显变化。结论橙皮素可能通过减轻氧化应激，降低MDA，升高SOD、TAOC，从而改善心衰大鼠的心脏功能。

心衰；橙皮素；异丙基肾上腺素；氧化应激；大鼠

Abstract:ObjectiveTo explore the protective effects and possible mechanisms of hesperetin against isoproterenol (ISO)-induced heart failure (HF) in rats.MethodsForty Sprague-Dawley (SD) rats were randomly divided into four groups：control group(group C)， hesperetin group (group H)， isoproterenol group (group I)and H+I group (group T). Rats in group I and group T were subcutaneously injected with ISO (150 mg/kg) once a day for 2 consecutive days.The model was successfully established in heart failure was determined by echocardiography after 2 weeks. Hesperetin was administered at the dosage of 100 mg/kg， po by gavage for a period of 10 days in group H and group T. Cardiac function of all rats including left ventricular end-diastolic diameter (LVEDD)， left ventricular end-systolic dimension (LVESD)， left ventricular ejection fractions (EF)， left ventricular fractional shortening (FS) was assessed by echocardiography. Collecting serum of all rats， malondialdehyde (MDA)，superoxide dismutase (SOD)， total antioxidant capacity (TAOC) were detected by thiobarbiturieacid colorimetry， WST-1 method and colorimetry method respectively.ResultsThere was not obvious changes of cardiac function in group C and group H. ISO inhibited the cardiac function of rats significantly including LVESD， EF， as well as FS， compared to group C(P<0.05). LVESD was increased while EF and FS were decreased. The level of MDA in group I was significantly higher (P<0.05) while the levels of SOD and TAOC were significantly lower than group C (P<0.05). Hesperetin attenuated the effect of heart failure induced by ISO. Cardiac function of rats including LVESD， EF，as well as FS was improved in group T compared to group I (P<0.05).LVESD was declined， EF and FS were ascended. The level of MDA was significantly lower，the levels of SOD，TAOC in group T were significantly higher than that in group I (P<0.05).ConclusionHesperetin can attenuate ISO-induced heart failure in rats. Its possible mechanisms may be associated with regulating oxidative stress.

Keywords：heart failure；hesperetin；isoproterenol；oxidative stress；rat

目前我国心脏疾病发病率和死亡率仍呈增高趋势，发病人群趋于年轻化，增加了社会经济负担，降低了人群平均寿命。各种心血管疾病的终末阶段即进展成为心衰，治疗效果差，死亡率高[1]。尽管目前症状性心衰的治疗有大量重要的进展，心衰死亡以及心衰相关的花费仍然在持续增加[2]。由于我国人口老龄化加速和包括糖尿病以及高血压等疾病患病率的增加，未来十年，心衰发病率仍会增加。活性氧信号在维持细胞生存和功能过程中发挥正常生理信号分子的作用，调节心血管信号的正常传导[3]，多项证据表明，氧化应激参与了心脏疾病的发生发展，过度的氧化应激诱导多种心血管疾病和状态，最终引发心衰。……