丹参酮ⅡA对压力负荷增加大鼠心肌纤维化的影响及机制  

Effect of tanshinone ⅡA on the expression of TNF-α and NF-κB in rats with pressure overload

作　　者：蔡辉[1] 蔡佳玉[1] 张静[1] 赵智明[1] 

机构地区：[1]南京军区南京总医院,南京210002

出　　处：《山东医药》2013年第9期14-16,F0003,共4页Shandong Medical Journal

基　　金：南京总医院科研基金面上项目(2010Q027)

摘　　要：目的探讨丹参酮ⅡA(TanⅡA)对压力负荷增加大鼠心肌纤维化的抑制作用及机制。方法将32只成年雄性SD大鼠随机分成假手术组、模型组、TanⅡA组及卡托普利组。后三组行肾上方腹主动脉缩窄术建立压力负荷增加心肌纤维化模型,假手术组仅分离腹主动脉而不结扎。造模后4周TanⅡA组腹腔注射TanⅡA 20 mg/(kg.d),卡托普利组予卡托普利100 mg/(kg.d)灌胃,均每天上午给药1次,连续给药4周;假手术组及模型组均不给药。8周后检测心脏质量指数和心肌组织病理学变化,ELISA法检测心肌羟脯氨酸(HYP)与血清TNF-α水平,免疫组化法检测心肌组织NF-κB p65蛋白表达。结果与假手术组比较,模型组心脏质量指数、心肌HYP表达及血清TNF-α和心肌组织NF-κB p65含量均升高(P均<0.01);与模型组比较,TanⅡA组的心脏质量指数、心肌HYP含量、血清TNF-α和心肌组织NF-κB p65水平均降低(P均<0.01)。结论 NF-κB信号介导的心肌炎症反应参与了压力负荷增加大鼠心肌纤维化的发生与发展。TanⅡA能抑制TNF-α和NF-κB信号通路而改善心肌纤维化。Objective To observe the changes of TNF-α and NF-KB expressions in rats with pressure overload and to explore the protective effects of tanshinone Ⅱ A （Tan Ⅱ A） on myocardial fibrosis. Methods Thirty-two SD rats induced by abdominal aorta constriction preparation were randomly divided into 4 groups, which were sham group, model group, Tan Ⅱ A group, and captopril group （ each n = 8 ）. The model of pressure overload-induced myocardial fibrosis was successfully established after 4 weeks of operation. After four weeks of Tan Ⅱ A treatment and 8 weeks later, heart mass indexes were estimated in concurrent evaluation of myocardial histology. Myocardial hydroxyproline content and serum TNF-α were meas- ured by method of ELISA. Immunohistochemistry was used to test myocardial NF-KB p65 content. Results Compared with sham group, heart mass indexes, myocardial hydroxyproline content, serum TNF-ct and myocardial NF-KB p65 content in- creased in the model group （ P 〈 0.01 ）. Compared with model group, heart mass indexes, myocardial hydroxyproline con- tent, serum TNF-α and myocardial NF-KB p65 content decreased in the Tan Ⅱ A group （ P 〈 0.01 ）. Conclusions The expressions of serum TNF-α and myocardial NF-KB p65 protein significantly increased in pressure overload rat myocardium, indicating that TNF-α and NF-KB signaling mediated myocardial inflammation in the pressure overload in rat myocardial fi- brosis and development. Tan Ⅱ A could alleviate myocardial fibrosis by inhibition of TNF-α and NF-KB signaling pathway.

关 键 词：丹参酮ⅡA 压力负荷 心肌纤维化 肿瘤坏死因子-Α 核转录因子-ΚB 

分 类 号：R364.3[医药卫生—病理学]