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丹参酮ⅡA对压力负荷增加大鼠心肌肥厚的抑制作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第3期
页码:
311-316
栏目:
基础研究
出版日期:
2013-06-25

文章信息/Info

Title:
Protective effect of tanshinone ⅡA against myocardial hypertrophy in rats with pressure overload
作者:
常文静; 赵凌杰; 赵智明; 沈思钰; 董晓蕾; 蔡 辉
(南京军区南京总医院中西医结合科，江苏 南京 210002)
Author(s):
CHANG Wenjing;  ZHAO Lingjie;  ZHAO Zhiming;  SHEN Siyu;  DONG Xiaolei;  CAI Hui
(Department of Integrated Traditional Chinese and Western Medicine, Nanjing General Hospital, Nanjing Military Area Command, Nanjing 210002, Jangsu, China)
关键词:
丹参酮ⅡA; 压力负荷; 心肌肥厚; RhoA/Rock信号通路; 大鼠
Keywords:
tanshinone II A;  pressure overload;  myocardial hypertrophy;  RhoA/Rock signaling pathway
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的:观察RhoA、Rock1蛋白在压力负荷增加大鼠心肌中的表达，探讨丹参酮ⅡA（tanshinone ⅡA，Tan II A）对压力负荷增加大鼠心肌肥厚的抑制作用。方法:40只成年雄性SD大鼠，随机分成5组（n=8），即假手术组（Sham组）、模型组（Model组）、Tan II A低剂量组［LTan II A组，10 mg/(kg·d)］、Tan II A高剂量组［H-Tan II A组，20 mg/(kg·d)］及阳性对照药物卡托普利组［Captopril组，100 mg/(kg·d)］。除Sham组外，其余4组大鼠均行肾上方腹主动脉缩窄术建立压力负荷增加心肌肥厚模型，Sham组大鼠仅分离腹主动脉而不结扎。术后4周成功造模并开始给药，疗程为4周。8周后，检测心脏肥厚指数和心肌组织病理学，ELISA法检测心肌羟脯氨酸含量以及免疫组化和免疫印迹法检测心肌组织中RhoA和Rock1蛋白的含量。结果:与Sham组比较，Model组大鼠的心脏肥厚指数、心肌羟脯氨酸含量及心肌组织中RhoA和Rock1蛋白含量均显著升高（均P<0.01）；与Model组比较，Tan II A低剂量组的心脏肥厚指数、心肌羟脯氨酸含量及心肌组织中RhoA和Rock1蛋白含量均降低（均P<0.05），而Tan II A高剂量组上述指标均显著降低（均P<0.01）。结论:压力负荷增加大鼠心肌组织中RhoA和Rock1蛋白的表达明显升高，表明RhoA/Rock信号通路参与了压力负荷增加大鼠心肌肥厚的发生与发展。Tan II A能抑制RhoA/Rock信号通路，从而改善心肌肥厚。
Abstract:
AIM:To observe the changes of RhoA and Rock1 expressions in rat myocardial tissues with pressure overload and to explore the protective effects of tanshinone II A (Tan II A) against myocardial hypertrophy. METHODS: Thirtytwo SpragueDawley (SD) rats induced by abdominal aorta constriction preparation were randomly divided into 4 groups (each, n=8): Model group (P<001), Tan II A of low dose group ［LTan Ⅱ A group, 10 mg/(kg·day)］, Tan II A of high dose group ［HTan Ⅱ A group, 20 mg/(kg·day)］, positive captopril group ［captopril group, 100 mg/(kg·day)］ and age matched SD sham operated group (n=8) as control. The model of pressure overloadinduced myocardial fibrosis was successfully established after 4 weeks of operation. After four weeks of Tan II A treatment, heart mass indexes were estimated, in concurrent evaluation of myocardial histology, as well as myocardial hydroxyproline content by ELISA, and immunohistochemistry staining and Western blot for myocardial RhoA and Rock1 content. RESULTS: Compared with those in Sham group, heart mass indexes, myocardial hydroxyproline content and myocardial RhoA and Rock1 content were increased in the Model group (P<001); Compared with those in Model group, heart mass indexes, myocardial hydroxyproline content and myocardial RhoA and Rock1 content were decreased in the LTan Ⅱ A group (P<005), while these indexes were decreased significantly in the HTan Ⅱ A group(P<001). CONCLUSIONS: The expressions of RhoA and Rock1 protein significantly increase in pressure overload rat myocardium, indicating that RhoA/Rock signaling pathways are involved in the pressure overload in rat cardiac hypertrophy and occurrence and development of cardiac hypertrophy in rats with pressure overload. Tan II A can alleviate cardiac hypertrophy possibly by downregulation of the expression of RhoA/Rock signaling pathways.

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备注/Memo

备注/Memo:
收稿日期：2012-11-15.
基金项目：南京总医院科研基金面上课题资助（2010Q027）
通讯作者：蔡辉，主任医师，主要从事中西医结合临床与基础研究Email：njzy_caihui@163.com
作者简介：常文静，硕士生Email：changwenjing_8@126.com
更新日期/Last Update: 2013-07-16