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丁苯酞对慢性心力衰竭大鼠心功能、氧化应激及心肌细胞凋亡的影响
作者:钟斌  冉苒 
单位:重庆市涪陵中心医院, 重庆 涪陵 408000
关键词:丁苯酞 慢性心力衰竭 异丙肾上腺素 心功能 氧化应激 凋亡 大鼠 
分类号:R541.6;R-33
出版年·卷·期(页码):2020·39·第五期(563-568)
摘要:

目的:探讨丁苯酞对慢性心力衰竭(以下简称心衰)大鼠心功能、氧化应激及心肌细胞凋亡的影响。方法:皮下注射异丙肾上腺素构建慢性心衰大鼠模型,将造模成功的大鼠随机分为模型组、低剂量组、高剂量组3组,选取皮下注射PBS的大鼠作为对照组。低剂量组和高剂量组每日分别给予20、80 mg·kg-1的丁苯酞灌胃,对照组和模型组每日给予等体积的PBS灌胃,共给药4周。检测各组大鼠心功能、心重指数以及心脏组织中丙二醛(MDA)、超氧化物歧化酶(SOD)的含量;TUNEL染色法检测心肌细胞的凋亡;蛋白质印迹法检测凋亡相关蛋白和Nrf2/ARE信号通路的表达。结果:与模型组相比,低剂量组和高剂量组的左室收缩压(LVSP)、左心室内压最大上升速率(+dp/dtmax)、SOD升高,左室舒张末压(LVEDP)、左心室内压最大下降速率(-dp/dtmax)、心重指数、MDA含量降低(P<0.05),TUNEL阳性染色明显较弱,Bax和Active caspase-3的表达降低,Bcl-2、Nrf2和HO-1的表达升高(P<0.05);高剂量组优于低剂量组(P<0.05)。结论:丁苯酞可以改善异丙肾上腺素诱导慢性心衰大鼠模型的心功能,降低氧化应激水平,抑制心肌细胞凋亡,可能与激活Nrf2/ARE信号通路有关。

Objective: To explore the influence of butylphthalide on cardiac function, oxidative stress and myocardial apoptosis in rats with chronic heart failure.Methods: Isoproterenol was injected subcutaneously to construct chronic heart failure rats. The rats with successful modeling were randomly divided into three groups:model group, low-dose group and high-dose group. Rats injected with PBS subcutaneously were selected as control group.Rats in the low-dose group and high-dose group were given 20 and 80 mg·kg-1 butylphthalide by gavage every day respectively. The control group and model group were given PBS with the same volume by gavage every day. The drug was administered for 4 weeks.Cardiac function, cardiac weight index and the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in heart tissues were measured.TUNEL staining was used to detect apoptosis in cardiomyocytes. The expression of apoptosis-related proteins and Nrf2/ARE signaling pathway were detected by Western blotting. Results: Compared with model group, left ventricular systolic pressure (LVSP), maximum rate of rise of left ventricular pressure (+dp/dtmax) and SOD in the low-dose group and high-dose group increased (P<0.05); left ventricular end-diastolic pressure (LVEDP), maximum rate of fall of left ventricular pressure (-dp/dtmax), cardiac weight index, MDA decreased (P<0.05); TUNEL positive staining decreased significantly; the expression of Bax and Active caspase-3 decreased (P<0.05); the expression of Bcl-2, Nrf2 and HO-1 increased (P<0.05).The above indexes in the high-dose group were better than those of the low-dose group (P<0.05). Conclusion: Butylphthalide can improve cardiac function, reduce oxidative stress and inhibit cardiomyocyte apoptosis in rats with chronic heart failure induced by isoprenaline, which may be related to activation of Nrf2/ARE signaling pathway.

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