丹酚酸A对压力超负荷大鼠心功能减退和心室重构的改善作用
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Improving effect of salvianolic acid A on pressure overload-induced cardiac dysfunction and ventricular remodeling in rats
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    目的:探讨丹酚酸A(Sal A)对压力超负荷大鼠心功能减退和心室重构的改善作用-方法:采用主动脉缩窄法(TAC)制备压力超负荷大鼠模型,并连续给予5 mg/(kg-d)的Sal A灌胃处理,同时部分压力超负荷大鼠仅注射等体积的生理盐水(saline),假手术(Sham)仅行开胸处理而不行TAC,依据实验设计将大鼠分为4组:Sham-saline组-TAC-saline组-Sham-Sal A组和TAC-Sal A组-分析12周后4组的血流动力学-心功能-心脏解剖学指标;采用HE-Masson’s三重及特异性荧光探针DHE染色分析心肌细胞的形态学-纤维化及活性氧自由基水平;免疫印迹法检测心肌细胞凋亡相关基因的蛋白水平-结果:与Sham-saline组比较,TAC处理可导致心率-左室收缩期平均压力-左室内压最大上升速率-Bcl-2(抑制凋亡基因)水平降低(P < 0.05),左室舒张末期压力-心肌直径-胶原容积分数-心脏体重比-心肌荧光强度-Bax和Cleaved caspase-3(促凋亡基因)水平升高;给予Sal A处理的压力超负荷大鼠,以上指标均获改善,且差异有统计学意义;但左室收缩期平均压力-心脏体重比-心肌直径-胶原容积分数-凋亡相关基因的水平仍与Sham-saline组有差异(P < 0.05);Sal A处理对Sham大鼠的各项指标无影响-结论:Sal A可改善压力超负荷大鼠的心功能减退及包括心肌肥大-纤维化及凋亡在内的心室重构,具有较好的保护作用-

    Abstract:

    Objective:To explore the improving effect of Salvianolic acid A (Sal A) on pressure overload-induced cardiac dysfunction and ventricular remodeling in rats. Methods:The pressure overload rat model was established by transverse aortic constriction(TAC). The Sal A was applied at the concentration of 5 mg/(kg-d) by gavage for continuous 12 weeks,and some rats with pressure overload were treated with the same volume of saline. The rats were assigned into 4 groups:Sham-saline,TAC-saline,Sham-Sal A and TAC-Sal A. Twelve weeks later,hemodynamic conditions,heart function and heart anatomy indicators were analyzed among 4 groups. Hematoxylin-eosin (HE),Masson's triple staining and specific fluorescent probe DHE were performed to analyze the morphology,fibrosis and reactive oxygen species levels of myocardial cell. The protein levels of apoptosis related genes were evaluated by Western blotting. Results:Compared with the Sham-saline group,TAC operation led to a decrease of heart rate,mean left ventricular systolic pressure,left ventricular pressure maximal rate and protein level of Bcl-2 (anti-apoptosis gene),and an increase of left ventricular end-diastolic pressure,cardiac diameter,collagen volume fraction,heart weight ratio,myocardial fluorescence intensity and protein levels of Bax and Cleave caspase-3 (pro-apoptotic gene). After the treatment with Sal A,the above indicators got attenuated. However,there were still significant differences on mean systolic pressure of left ventricular,heart weight ratio,cardiac diameter,collagen volume fraction and protein levels of apoptosis-related genes between the group of Sham-saline and the group of TAC-Sal A(P < 0.05). The treatment with Sal A had no effect on the indicators of Sham rats. Conclusion:Sal A can improve pressure overload-induced cardiac dysfunction and attenuate and protect ventricular remodeling including myocardial hypertrophy,fibrosis and apoptosis.

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丁 超,谢利平,李荣成.丹酚酸A对压力超负荷大鼠心功能减退和心室重构的改善作用[J].南京医科大学学报(自然科学版),2014,(1):012-017

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  • 收稿日期:2013-07-25
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  • 在线发布日期: 2014-01-27
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