槲皮素可改善大鼠实验性自身免疫性心肌炎。

Quercetin ameliorates experimental autoimmune myocarditis in rats.

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.

出版信息

J Pharm Pharm Sci. 2010;13(3):311-9. doi: 10.18433/j3vs3s.

DOI:10.18433/j3vs3s

PMID:21092705

Abstract

PURPOSE

Experimental autoimmune myocarditis (EAM) in rats is an animal model of human giant cell myocarditis and post-myocarditis dilated cardiomyopathy. The pathogenesis of EAM has not been elucidated, but there is accumulating evidence that cytokines secreted from monocytes/macrophages and T cells play a crucial role in the induction and progression of disease. Flavonoids are a large group of polyphenolic compounds abundantly present in the human diet, which scavenge oxygen radicals and have anti-inflammatory activities. Having in mind in vivo beneficial effects of flavonoid quercetin in different animal models of immunoinflammatory diseases such as experimental autoimmune encephalomyelitis and adjuvant arthritis, on the one side, and its in vitro suppressive effect on production of tumor necrosis factor-alpha (TNF-α) on the other side, we investigated the effects of quercetin on EAM in rats.

METHODS

Myocarditis was induced in Dark Agouti (DA) rats by injection of porcine cardiac myosin and quercetin at doses of 10 or 20 mg/kg was orally administered from days 0 to 21 after induction of disease. The severity of myocarditis was evaluated by determination of heart weight/body weight ratio (Hw/Bw) and histopathological examination of hearts. The levels of cytokines (TNF-α, IL-12, IL-17 and IL-10) in serum and lymph node cells (LNC) culture supernatants were measured by ELISA.

RESULTS

The rats treated with 20 mg/kg of quercetin had significantly decreased incidence of EAM, Hw/Bw, macroscopic and microscopic scores of hearts. Further, in EAM rats treated with quercetin levels of TNF-α and IL-17 were significantly lower, while the level of IL-10 was significantly higher both in serum and culture supernatants of LNC stimulated with concanavalin A compared with vehicle-treated animals.

CONCLUSIONS

The present study suggests that quercetin ameliorates EAM, at least in part, by interfering production of proinflammatory (TNF-α and IL-17) and/or anti-inflammatory (IL-10) cytokines.

摘要

目的

实验性自身免疫性心肌炎（EAM）在大鼠中是人类巨细胞心肌炎和心肌炎后扩张型心肌病的动物模型。EAM 的发病机制尚未阐明，但有越来越多的证据表明，单核细胞/巨噬细胞和 T 细胞分泌的细胞因子在疾病的诱导和进展中起关键作用。类黄酮是一大类多酚化合物，在人类饮食中含量丰富，可清除氧自由基并具有抗炎活性。考虑到类黄酮槲皮素在实验性自身免疫性脑脊髓炎和佐剂性关节炎等免疫炎性疾病的不同动物模型中的体内有益作用，一方面，以及它在体外对肿瘤坏死因子-α（TNF-α）产生的抑制作用另一方面，我们研究了槲皮素对大鼠 EAM 的影响。

方法

通过注射猪心肌肌球蛋白诱导 Dark Agouti（DA）大鼠心肌炎，在疾病诱导后第 0 至 21 天给予 10 或 20mg/kg 的槲皮素口服给药。通过测定心脏重量/体重比（Hw/Bw）和心脏组织学检查评估心肌炎的严重程度。通过 ELISA 测定血清和淋巴结细胞（LNC）培养上清液中细胞因子（TNF-α、IL-12、IL-17 和 IL-10）的水平。