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X 芪苈强心口服液通过TGF-β1/Smad3和p38 MAPK信号通路改善慢性心力衰竭大鼠的心功能。

X indening oral liquid improves cardiac function of rats with chronic cardiac failure via TGF-ß1/Smad3 and p38 MAPK pathway.

作者信息

Wei Yunliang, Guo Changsheng, Zhao Jingsheng, Yang Jun, Yi Weiguo, Liu Hong, Lin Xinwei, Zhang Zhengchen

机构信息

Department of Cardiovascular Medicine, The 152nd Central Hospital of PLA, Pingdingshan, Henan 467000-China.

出版信息

Anatol J Cardiol. 2017 May;17(5):367-373. doi: 10.14744/AnatolJCardiol.2016.7438. Epub 2017 Jan 17.

Abstract

OBJECTIVE

Xindening oral liquid (Xin) is a widely used traditional Chinese medicine for the treatment of chronic heart failure (CHF). However, the exact mechanisms related to its therapeutic effects against CHF remain unclear. In the present study, we investigate the effects of Xin on cardiac function in CHF rats and the possible mechanisms involved.

METHODS

Transverse aortic constriction (TAC) was conducted to induce a CHF rat model in this study. Sixty male Wistar rats were randomly assigned to six groups 28 days after TAC: sham; CHF model; Xin at concentrations of 5 ml/kg, 10 mL/kg, and 20 mL/kg; and QiLi 0.6 g/kg. After four weeks, the rats were treated with Xin (5, 10, or 20 mL/kg/d) for six weeks consecutively. At the end of the study, the cardiac function, heart weight index (HWI) and left ventricular mass index (LVMI), serum level of LDH, B-type natriuretic peptide (BNP), cTnI and CK-MB, and collagen volume fraction were studied. The expression of transforming growth factor-ß1 (TGF-ß1), drosophila mothers against decapentaplegic protein 3 (Smad3), and p38 mitogen activated protein kinase (p38 MAPK) were detected.

RESULTS

The results showed that Xin treatment significantly improved cardiac function but decreased the serum level of LDH, BNP, cTnI, and CKMB of CHF rats. In addition, it reduced the HWI, LVMI, and collagen volume fraction compared with the model group. Xin treatment significantly improved cardiac function and attenuated cardiac fibrosis by suppressing the p38 MAPK and TGF-ß1/Smad3 signaling pathway in CHF rats.

CONCLUSION

These results suggested that Xin might be a promising complementary treatment for CHF. More detailed experimental studies will be carried out in our subsequent research.

摘要

目的

心宁定口服液(心)是一种广泛用于治疗慢性心力衰竭(CHF)的中药。然而,其治疗CHF的确切机制仍不清楚。在本研究中,我们研究了心对CHF大鼠心功能的影响及其可能的作用机制。

方法

本研究采用横向主动脉缩窄(TAC)法建立CHF大鼠模型。60只雄性Wistar大鼠在TAC术后28天随机分为6组:假手术组;CHF模型组;5 ml/kg、10 mL/kg和20 mL/kg浓度的心宁定组;以及0.6 g/kg的芪苈组。四周后,大鼠连续六周接受心宁定(5、10或20 mL/kg/d)治疗。在研究结束时,检测心功能、心脏重量指数(HWI)和左心室质量指数(LVMI)、血清乳酸脱氢酶(LDH)、B型利钠肽(BNP)、肌钙蛋白I(cTnI)和肌酸激酶同工酶(CK-MB)水平以及胶原容积分数。检测转化生长因子-β1(TGF-β1)、果蝇抗五聚体蛋白3(Smad3)和p38丝裂原活化蛋白激酶(p38 MAPK)的表达。

结果

结果表明,心宁定治疗可显著改善CHF大鼠的心功能,但降低其血清LDH、BNP、cTnI和CKMB水平。此外,与模型组相比,它降低了HWI、LVMI和胶原容积分数。心宁定治疗通过抑制CHF大鼠的p38 MAPK和TGF-β1/Smad3信号通路,显著改善心功能并减轻心肌纤维化。

结论

这些结果表明,心宁定可能是一种有前景的CHF辅助治疗药物。我们将在后续研究中进行更详细的实验研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f9/5469083/3010d70d60f1/AJC-17-367-g002.jpg

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