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玫瑰黄酮通过抑制JNK和p38 MAPK减轻小鼠心肌缺血再灌注损伤。

Rosa rugosa flavonoids alleviate myocardial ischemia reperfusion injury in mice by suppressing JNK and p38 MAPK.

作者信息

Zhang Xuehui, Wang Yuhui, Shen Wanli, Ma Shangzhi, Chen Wen, Qi Rong

机构信息

Shihezi University College of Pharmacy/Key Laboratory of Xinjiang Endemic Phytomedicine Resources Ministry of Education, Xinjiang, China.

Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University, Beijing, China.

出版信息

Microcirculation. 2017 Oct;24(7). doi: 10.1111/micc.12385.

Abstract

OBJECTIVE

Although Rosa rugosa has been applied for preventing coronary artery disease, the pharmacological mechanism is little explored. In this study, the effects and mechanisms of Rosa rugosa flavonoids (RRF) on myocardial ischemia reperfusion injury (MIRI) were investigated.

METHODS

Mice were pretreated by intragastric administration of 600 mg/kg RRF for 7 days. Then MIRI was induced by 45 minutes coronary artery ligation and 3 hours reperfusion. Myocardial infarct size (MIS) and histopathology, activities of myocardial enzymes, and effects of RRF on inflammation and apoptosis were evaluated.

RESULTS

Pretreating the mice with RRF significantly reduced MIS and inhibited activity of plasma myocardial enzymes. Activity of the enzymes associated with anti-oxidation, SOD, and TEAC, and mRNA expression of NOX2 were significantly elevated. RRF pretreatment significantly decreased the translocation of p65 from the cytoplasm into the nucleus and reduced the expression of the pro-inflammatory cytokines, IL-6 and IL-1β. RRF pretreatment also significantly prevented the expression of caspase-3 and Bax, and increased the expression of Bcl-2. And RRF inhibited the phosphorylation of JNK and p38 MAPK.

CONCLUSIONS

RRF significantly inhibited MIRI through anti-oxidative, anti-inflammatory, and anti-apoptosis effects, and mechanisms were associated with its inhibition on phosphorylation of JNK and p38 MAPK.

摘要

目的

虽然玫瑰已被应用于预防冠状动脉疾病,但其药理机制鲜有研究。本研究探讨了玫瑰黄酮(RRF)对心肌缺血再灌注损伤(MIRI)的影响及机制。

方法

小鼠经灌胃给予600mg/kg RRF预处理7天。然后通过冠状动脉结扎45分钟和再灌注3小时诱导MIRI。评估心肌梗死面积(MIS)和组织病理学、心肌酶活性以及RRF对炎症和凋亡的影响。

结果

用RRF预处理小鼠可显著降低MIS并抑制血浆心肌酶活性。与抗氧化相关的酶SOD和TEAC的活性以及NOX2的mRNA表达显著升高。RRF预处理显著降低p65从细胞质向细胞核的转位,并降低促炎细胞因子IL-6和IL-1β的表达。RRF预处理还显著抑制caspase-3和Bax的表达,并增加Bcl-2的表达。并且RRF抑制JNK和p38 MAPK的磷酸化。

结论

RRF通过抗氧化、抗炎和抗凋亡作用显著抑制MIRI,其机制与其对JNK和p38 MAPK磷酸化的抑制作用有关。

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