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七芍五味方对柯萨奇 B3 病毒诱导的小鼠病毒性心肌炎的心脏保护作用机制。

The heart-protective mechanism of Qishaowuwei formula on murine viral myocarditis induced by CVB3.

机构信息

Pediatric Department of Provincial Hospital affiliated to Shandong University, 324 Jing Wu Road, Jinan, Shandong 250021, China.

出版信息

J Ethnopharmacol. 2010 Feb 3;127(2):221-8. doi: 10.1016/j.jep.2009.11.017. Epub 2009 Nov 20.

DOI:10.1016/j.jep.2009.11.017
PMID:19932162
Abstract

AIM OF STUDY

The heart-protective effect and mechanism of Qishaowuwei formula (QSW), a Traditional Chinese Medicine formula composed of Radix Astragali, Radix Paeoniae Rubra and Fructus Schisandrae was investigated on murine model of viral myocarditis (VMC) induced by Coxsackievirus B3 (CVB3).

MATERIALS AND METHODS

Mice were randomly divided into infected control group, QSW high dose group, QSW medium dose group, QSW low dose group and Vitamin C plus Ribavirin treatment group. 50 mice were included in each group. The day of virus inoculation was defined as day 0 and the drug treatment continued once a day for 14 days. Mice were sacrificed on days 3, 7, 14, 21 postinoculation (p.i.). The histopathological changes of myocardium, CVB3 RNA copies in the myocardium, cardiomycytic apoptosis, the serum level of superoxide dismutase (SOD) and maleic dialdehyde (MDA) and the phenotype of T lymphocytes subsets in peripheral blood was analyzed.

RESULTS

QSW treatment significantly increase the survival rate (p<0.05) in VMC model. Histopathology and flow cytometry inspection revealed low ratio of cardiomyocytes necrosis and apoptosis in QSW treated mice with dose dependent manner. The cardiomyocytic ultra-structure observed by transmission electron microscope also supported the above results. The ameliorated tissue damage was consistent with reduced CVB3 copy numbers detected by real-time PCR in the myocardium of QSW treated mice. The antioxidant effect of QSW was proved by elevated activity of SOD and reduced level of MDA in the serum. Furthermore, the disturbed balance of CD4+ and CD8+ subsets in peripheral blood was restored.

CONCLUSION

These results demonstrated QSW had potent protective effect against CVB3-induced heart injury and this effect might be mediated by its inhibition on viral replication, antioxidant activity and immunoregulation mechanism.

摘要

目的

研究由黄芪、赤芍和五味子组成的中药方剂七芍五味方(QSW)对柯萨奇病毒 B3(CVB3)诱导的病毒性心肌炎(VMC)小鼠模型的心脏保护作用及其机制。

材料与方法

将小鼠随机分为感染对照组、QSW 高剂量组、QSW 中剂量组、QSW 低剂量组和维生素 C 加利巴韦林治疗组,每组 50 只。病毒接种日定义为第 0 天,药物治疗每天 1 次,持续 14 天。接种后第 3、7、14、21 天处死小鼠。分析心肌组织的组织病理学变化、心肌中的 CVB3 RNA 拷贝数、心肌细胞凋亡、血清中超氧化物歧化酶(SOD)和丙二醛(MDA)水平以及外周血 T 淋巴细胞亚群的表型。

结果

QSW 治疗显著提高 VMC 模型的存活率(p<0.05)。组织病理学和流式细胞术检查显示,QSW 治疗组心肌细胞坏死和凋亡比例降低,呈剂量依赖性。透射电镜观察的心肌细胞超微结构也支持了上述结果。实时 PCR 检测到 QSW 治疗组心肌中 CVB3 拷贝数减少,与组织损伤改善一致。血清中 SOD 活性升高和 MDA 水平降低证明了 QSW 的抗氧化作用。此外,外周血中 CD4+和 CD8+亚群的失衡得到恢复。

结论

这些结果表明,QSW 对 CVB3 诱导的心脏损伤具有强大的保护作用,其作用机制可能与其抑制病毒复制、抗氧化活性和免疫调节有关。

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