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丹红注射液通过调节p38和NF-κb信号通路减轻异丙肾上腺素诱导的心肌肥大。

Danhong injection attenuates isoproterenol-induced cardiac hypertrophy by regulating p38 and NF-κb pathway.

作者信息

Mao Hao-Ping, Wang Xing-Ye, Gao Yun Hang, Chang Yan-Xu, Chen Lu, Niu Zi-Chang, Ai Ju-Qing, Gao Xiu-Mei

机构信息

Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

J Ethnopharmacol. 2016 Jun 20;186:20-29. doi: 10.1016/j.jep.2016.03.015. Epub 2016 Mar 9.

DOI:10.1016/j.jep.2016.03.015
PMID:26970569
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Danhong injection (DHI), derived from Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Salvia militiorrhiza Bunge), is an extensively-used Chinese material standardized clinical product for treatment of cardiovascular diseases.

AIM OF THE STUDY

Cardiac hypertrophy (CH) is an adaptive response of cardiomyocytes. Long-lasting cardiac hypertrophy results in the loss of compensation by cardiomyocytes which could ultimately develop into heart failure. In the present study, we aimed to investigate the effect and exact mechanisms of DHI on isoproterenol (ISO)-induced CH.

MATERIALS AND METHODS

H9c2 cells and male Wistar rats were stimulated by ISO in the present study to establish CH models in vitro and in vivo. CCk-8 assay, Western blot, real time-polymerase chain reaction (RT-PCR), electrophoretic mobility shift assay (EMSA) and Echocardiography were used in the present study.

RESULTS

DHI significantly attenuated ISO-induced CH of H9c2 cells (p<0.01). DHI decreased ISO-induced atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) elevation both at the mRNA and protein levels (p<0.05 and p<0.01, respectively). Western blot showed that DHI down-regulated the phosphorylation of p38. Furthermore, we found that DHI inhibited the nuclear translocation and activation of NF-κb. Echocardiography from ISO-induced CH rats showed that DHI significantly decreased left ventricle (LV) mass, the thickness of the LV end-systolic posterior wall (LVPWs), and the LV end-diastolic posterior wall (LVPWd) elevated by ISO (p<0.01 and p<0.05, respectively).

CONCLUSION

These data demonstrate that DHI might exert anti-cardiac hypertrophic effects by regulating p38 and NF-κb pathway.

摘要

民族药理学相关性

丹红注射液(DHI)由丹参(唇形科植物丹参Salvia miltiorrhiza Bge.,中药名为丹参)和红花(菊科植物红花Carthamus tinctorius L.)制成,是一种广泛应用于治疗心血管疾病的标准化中药临床产品。

研究目的

心肌肥大(CH)是心肌细胞的一种适应性反应。长期的心肌肥大导致心肌细胞失去代偿能力,最终可能发展为心力衰竭。在本研究中,我们旨在探讨丹红注射液对异丙肾上腺素(ISO)诱导的心肌肥大的作用及确切机制。

材料与方法

在本研究中,使用H9c2细胞和雄性Wistar大鼠,通过ISO刺激在体外和体内建立心肌肥大模型。本研究采用CCk-8法、蛋白质免疫印迹法、实时聚合酶链反应(RT-PCR)、电泳迁移率变动分析(EMSA)和超声心动图检查。

结果

丹红注射液显著减轻了ISO诱导的H9c2细胞心肌肥大(p<0.01)。丹红注射液在mRNA和蛋白质水平上均降低了ISO诱导的心房利钠肽(ANP)和脑利钠肽(BNP)升高(分别为p<0.05和p<0.01)。蛋白质免疫印迹法显示丹红注射液下调了p38的磷酸化水平。此外,我们发现丹红注射液抑制了NF-κb的核转位和激活。ISO诱导的心肌肥大大鼠的超声心动图显示,丹红注射液显著降低了ISO升高的左心室(LV)质量、左心室收缩末期后壁厚度(LVPWs)和左心室舒张末期后壁厚度(LVPWd)(分别为p<0.01和p<0.05)。

结论

这些数据表明,丹红注射液可能通过调节p38和NF-κb信号通路发挥抗心肌肥大作用。

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