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[中药血府逐瘀汤对血管紧张素II诱导的大鼠心脏成纤维细胞增殖及细胞外基质合成的影响]

[Effects of Chinese herbal medicine Xuefu Zhuyu Decoction on angiotensin II-induced proliferation and extracellular matrix synthesis of rat cardiac fibroblasts].

作者信息

Shen Yan, Wei Hong, Jin Chun-Lan

机构信息

Department of Cardiology, Yueyang Hospital of Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.

出版信息

Zhong Xi Yi Jie He Xue Bao. 2011 Mar;9(3):313-9. doi: 10.3736/jcim20110313.

DOI:10.3736/jcim20110313
PMID:21419085
Abstract

OBJECTIVE

To investigate the effects of Xuefu Zhuyu Decoction, a compound Chinese herbal medicine, on the proliferation and extracellular matrix synthesis of cardiac fibroblasts (CFs) from neonatal rats induced by angiotensin II, and to explore the mechanism of Xuefu Zhuyu Decoction in improving myocardial fibrosis.

METHODS

CFs derived from neonatal rats were cultured with enzymatic dissociation to establish a cell model of cardiac fibrosis induced by angiotensin II in vitro. CFs were divided into 6 groups, including blank control group, angiotensin II group, valsartan-medicated serum group, and 5%, 10% and 15% Xuefu Zhuyu decoction-medicated serum group. CFs in the blank control group were incubated with normal rat serum; CFs in the other groups were stimulated with angiotensin II at a dose of 10-6 mol/L, and then incubated with normal rat serum and 5%, 10% and 15% Xuefu Zhuyu decoction-medicated serum for 24 h, respectively. Methyl thiazolyl tetrazolium assay was employed to measure CF proliferation, and collagen synthesis was detected by analysis of the hydroxyproline in CFs. Radioimmunoassay was used to measure concentrations of procollagen III and hyaluronic acid. Enzyme-linked immunosorbent assay was used to measure fibronectin expression.

RESULTS

Compared with the blank control group, angiotensin II induced cardiac fibroblast proliferation, stimulated DNA and collagen syntheses (P<0.01), and increased fibronectin, hyaluronic acid and procollagen III concentrations (P<0.01). Xuefu Zhuyu decoction-medicated serum inhibited CF proliferation and DNA and collagen syntheses (P<0.05), and decreased the concentrations of fibroectin, hyaluronic acid and procollagen III (P<0.01).

CONCLUSION

Angiotensin II can induce cardiac fibrosis, stimulate cardiac fibroblast proliferation and extracellular matrix synthesis, while Xuefu Zhuyu Decoction can prevent cardiac fibrosis, the mechanism of which may be related to inhibiting CF proliferation and extracellular matrix synthesis.

摘要

目的

研究中药复方血府逐瘀汤对血管紧张素II诱导的新生大鼠心脏成纤维细胞(CFs)增殖及细胞外基质合成的影响,探讨血府逐瘀汤改善心肌纤维化的作用机制。

方法

采用酶解法培养新生大鼠来源的CFs,建立血管紧张素II诱导的体外心脏纤维化细胞模型。将CFs分为6组,包括空白对照组、血管紧张素II组、缬沙坦含药血清组以及5%、10%和15%血府逐瘀汤含药血清组。空白对照组用正常大鼠血清孵育;其他组用10-6 mol/L血管紧张素II刺激,然后分别用正常大鼠血清以及5%、10%和15%血府逐瘀汤含药血清孵育24 h。采用甲基噻唑基四氮唑法检测CFs增殖,通过分析CFs中羟脯氨酸含量检测胶原合成。采用放射免疫法检测III型前胶原和透明质酸浓度。采用酶联免疫吸附法检测纤连蛋白表达。

结果

与空白对照组相比,血管紧张素II诱导心脏成纤维细胞增殖,刺激DNA和胶原合成(P<0.01),并增加纤连蛋白、透明质酸和III型前胶原浓度(P<0.01)。血府逐瘀汤含药血清抑制CFs增殖及DNA和胶原合成(P<0.05),并降低纤连蛋白、透明质酸和III型前胶原浓度(P<0.01)。

结论

血管紧张素II可诱导心脏纤维化,刺激心脏成纤维细胞增殖及细胞外基质合成,而血府逐瘀汤可预防心脏纤维化,其机制可能与抑制CFs增殖及细胞外基质合成有关。

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