肝X受体抑制乳鼠心肌细胞缺氧/复氧损伤  

Liver X receptors attenuate anoxia/reoxygenation injury in neonatal rat cardiomyocytes

作　　者：殷然[1] 王梦洪[1] 郑泽琪[1] 彭锦添[1] 夏莺[2] 

机构地区：[1]南昌大学第一附属医院心内科江西省高血压病研究所 [2]江西省人民医院干部病房,江西南昌330006

出　　处：《中国病理生理杂志》2011年第9期1671-1675,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81000071)

摘　　要：目的:探讨肝X受体(LXRs)对乳鼠心肌细胞缺氧/复氧(A/R)损伤的影响和相应的细胞信号通路。方法:分离培养乳鼠心肌细胞,复制A/R模型;不同浓度LXRs激动剂T0901317(1、5、10μmol/L)预处理后,常规比色法检测复氧24 h后各组上清液乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性;real-time PCR检测各组细胞肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和单核细胞趋化因子-1(MCP-1)mRNA表达;心肌特异性表达LXRα及LXRβ的腺病毒载体转染H9c2细胞,随后进行A/R实验,荧光素酶报告基因法测定各组核因子-κB(NF-κB)活性。结果:T0901317预处理显著减轻A/R损伤引起的LDH和CK活性升高(P<0.05);与对照组比较,T0901317预处理组心肌细胞炎症因子释放显著减少(P<0.05);LXRs过表达明显抑制A/R损伤造成的H9c2细胞NF-κB活化。结论:LXRs是机体抗心肌缺血/再灌注损伤的重要防御因子。AIM： To investigate the effect of liver X receptors（LXRs） on anoxia/reoxygenation injury in cultured neonatal rat cardiomyocytes and to explore the underlying cellular signaling pathway.METHODS： Neonatal rat cardiomyocytes were cultured and treated with anoxia/reoxygenation in the absence or presence of T0901317（an agonist of LXRs） at various doses（1, 5 and 10 μmol/L）.LDH and CK were detected by colorimetry 24 h after reoxygenation.The relative transcription levels of proinflammatory factors,such as tumor necrosis factor α（TNF-α）,interleukin-6（IL-6） and monocyte chemoattractant protein-1（MCP-1）,were quantified by real-time PCR.H9c2 cells were infected with adenoviral vectors containing constitutively-active forms of LXRα and LXRβ,then underwent anoxia/reoxygenation procedure.The activity of NF-κB in the cells was detected by luciferase assay.RESULTS： Treatment with T0901317 significantly suppressed anoxia/reoxygenation-induced increases in LDH and CK（P0.05）.Transcription levels of proinflammatory factors in T0901317 treatment groups were significantly lower than those in control group（P0.05）.Adenovirus-mediated overexpression of constitutively-active LXRs suppressed anoxia/reoxygenation-induced NF-κB activity in H9c2 cells.CONCLUSION： LXRs are negative regulators of myocardial ischemia-reperfusion injury.

关 键 词：X受体 肝 心肌缺血/再灌注损伤 细胞培养 

分 类 号：R363[医药卫生—病理学]