Zhang Jia-Ying, Yang Zheng, Fang Kun, Shi Zhan-Li, Ren Dan-Hong, Sun Jing
Department of Critical Care Medicine, Hang Zhou Red Cross Hospital, Hangzhou 310014, Zhejiang, China.
Department of Critical Care Medicine, Hang Zhou Red Cross Hospital, Hangzhou 310014, Zhejiang, China.
Int Immunopharmacol. 2017 Jul;48:187-195. doi: 10.1016/j.intimp.2017.05.013. Epub 2017 May 16.
Oleuropein (OLE) is a natural secoiridoid that is derived from Olea europaea. OLE possesses cardioprotective effects in experimental models of hypertension, myocardial infarction, atherosclerosis and hyperlipidaemia. In the present study, the effects of OLE on experimental autoimmune myocarditis (EAM) were evaluated. EAM in rats were induced by subcutaneous injections of porcine cardiac myosin. Cardiac function parameters, myocardial pathology, myocardial inflammatory cell infiltration and nuclear factor kappa-B (NF-κB) expression were measured. Our data showed that the postmyocarditis rats exhibited increased left ventricular end systolic diameters, left ventricular end diastolic diameters, left ventricular end-diastolic pressures (LVEDP), and decreased ejection fractions. However, OLE significantly suppressed these changes in EAM rats. Histological analysis revealed that myosin induced miliary foci of discolouration on endocardial surfaces and extensive myocardial injuries with inflammatory cell infiltration were significantly improved by OLE therapy. A definitive positive correlation between the histological scores and LVEDP was observed. Moreover, OLE inhibited CD4, CD8 cells and macrophage infiltration in myocardium and decreased the serum production of tumour necrosis factor-a (TNF-a), interleukin-1β (IL-1β) and IL-6 in EAM rats. Expectedly, the myocardial levels of NF-κB p65, p-IκBa, IKKa were significantly attenuated by OLE, indicating the inhibitory effects of OLE on the NF-κB pathway. Furthermore, OLE decreased the myocardial expressions of phosphorylated-p38 MAPK, phosphorylated-ERK, and did not change the levels of p38 MAPK and ERK in EAM rats. Collectively, our results suggest that OLE effectively prevents the development of myocarditis, at least in part, by inhibiting the MAPKs and NF-κB mediated inflammatory responses.
橄榄苦苷（OLE）是一种天然的裂环环烯醚萜苷，来源于油橄榄。OLE在高血压、心肌梗死、动脉粥样硬化和高脂血症的实验模型中具有心脏保护作用。在本研究中，评估了OLE对实验性自身免疫性心肌炎（EAM）的影响。通过皮下注射猪心肌肌凝蛋白诱导大鼠发生EAM。测量心脏功能参数、心肌病理学、心肌炎性细胞浸润和核因子κB（NF-κB）表达。我们的数据显示，心肌炎后大鼠的左心室收缩末期直径、左心室舒张末期直径、左心室舒张末期压力（LVEDP）增加，射血分数降低。然而，OLE显著抑制了EAM大鼠的这些变化。组织学分析显示，肌凝蛋白诱导的心内膜表面粟粒状变色病灶以及伴有炎性细胞浸润的广泛心肌损伤通过OLE治疗得到显著改善。观察到组织学评分与LVEDP之间存在明确的正相关。此外，OLE抑制EAM大鼠心肌中CD4、CD8细胞和巨噬细胞浸润，并降低血清肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和IL-6的产生。不出所料，OLE显著降低了心肌中NF-κB p65、p-IκBa、IKKa的水平，表明OLE对NF-κB信号通路具有抑制作用。此外，OLE降低了EAM大鼠心肌中磷酸化-p38 MAPK、磷酸化-ERK的表达，而p38 MAPK和ERK的水平未发生变化。总体而言，我们的结果表明，OLE至少部分地通过抑制MAPKs和NF-κB介导的炎症反应有效预防心肌炎的发展。
