目的研究特异性敲除心肌白细胞介素-8(interleukin⁃8,IL⁃8)抑制信号转导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)活化改善慢性心力衰竭(CHF)小鼠心功能及炎症反应。方法野生型(WT)雄性小鼠分为WT对...目的研究特异性敲除心肌白细胞介素-8(interleukin⁃8,IL⁃8)抑制信号转导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)活化改善慢性心力衰竭(CHF)小鼠心功能及炎症反应。方法野生型(WT)雄性小鼠分为WT对照组、WT模型组,心肌特异性IL⁃8敲除(KO)雄性小鼠分为KO对照组、KO模型组,采用腹主动脉缩窄法建立CHF模型。采用超声心动图及血清中N末端脑钠肽(BNP)前体评价心功能,检测白介素⁃1β(IL⁃1β)、干扰素⁃γ(IFN⁃γ)、肿瘤坏死因子⁃α(tumor necrosis factor⁃α,TNF⁃α)的水平,IL⁃8、p⁃STAT3的表达水平。结果WT模型组心肌中出现了CHF的病理改变,心功能弱于WT对照组,IL⁃1β、IFN⁃γ、TNF⁃α的水平及IL⁃8、p⁃STAT3蛋白表达水平均高于对照组(P<0.05);特异性敲除IL⁃8并进行CHF造模,KO模型组心肌中CHF病理改变明显减轻,心肌中不表达IL⁃8,心功能优于WT模型组,IL⁃1β、IFN⁃γ、TNF⁃α的水平及p⁃STAT3的蛋白表达水平均低于WT模型组(P<0.05)。结论心肌特异性IL⁃8敲除显著改善CHF小鼠的心功能及心肌炎症反应,抑制STAT3磷酸化活化是与之相关的分子机制。展开更多
Background Whether pre-treatment with peroxisome proliferator activated receptor-γ （PPAR-γ） agonist has beneficial effect on myocardial ischemia / reperfusion （I/R） injury is not well established. In this study,...Background Whether pre-treatment with peroxisome proliferator activated receptor-γ （PPAR-γ） agonist has beneficial effect on myocardial ischemia / reperfusion （I/R） injury is not well established. In this study, we try to explore the cardioprotective effect of the pre-treatment with PPAR-γ agonist rosiglitazone （Ros） on the hearts suffering I/R injury. Methods Experimental I/R injury was induced by Langendorff heart reperfusion model and left anterior descending artery ligation in rats. Oxidative stress was evaluated by measuring lactate dehydrogenase （LDH）, nitric oxide synthase （NOS）, superoxide dismutase （SOD） and malonaldehyde （MDA）. Bcl-2 and Bax were detected by Western blotting and real-time PCR. Results Ros treatment significantly decreased SOD and inducible nitric oxide synthase and increased creatine kinase, LDH, MDA, and endothelial nitric oxide synthase in-vivo. Both in vitro and in-vivo, Ros treatment increased Bcl-2 level and decreased Bax level in a dose-dependent manner. In vitro, Ros treatment significantly increased SOD but lowered MDA and LDH in a dose-dependent manner. Conclusions Pre-treatment with PPARγ agonist Ros has beneficial effect on myocardial I/R injury by attenuating oxidative stress and inhibiting cardiomyocyte apoptosis.展开更多
文摘目的研究特异性敲除心肌白细胞介素-8(interleukin⁃8,IL⁃8)抑制信号转导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)活化改善慢性心力衰竭(CHF)小鼠心功能及炎症反应。方法野生型(WT)雄性小鼠分为WT对照组、WT模型组,心肌特异性IL⁃8敲除(KO)雄性小鼠分为KO对照组、KO模型组,采用腹主动脉缩窄法建立CHF模型。采用超声心动图及血清中N末端脑钠肽(BNP)前体评价心功能,检测白介素⁃1β(IL⁃1β)、干扰素⁃γ(IFN⁃γ)、肿瘤坏死因子⁃α(tumor necrosis factor⁃α,TNF⁃α)的水平,IL⁃8、p⁃STAT3的表达水平。结果WT模型组心肌中出现了CHF的病理改变,心功能弱于WT对照组,IL⁃1β、IFN⁃γ、TNF⁃α的水平及IL⁃8、p⁃STAT3蛋白表达水平均高于对照组(P<0.05);特异性敲除IL⁃8并进行CHF造模,KO模型组心肌中CHF病理改变明显减轻,心肌中不表达IL⁃8,心功能优于WT模型组,IL⁃1β、IFN⁃γ、TNF⁃α的水平及p⁃STAT3的蛋白表达水平均低于WT模型组(P<0.05)。结论心肌特异性IL⁃8敲除显著改善CHF小鼠的心功能及心肌炎症反应,抑制STAT3磷酸化活化是与之相关的分子机制。
基金supported by the National Natural Science Foundation of China(No.81301676)Guangdong Province Natural Science Fund(S2011010002650)+1 种基金Guangdong Provincial Science and Technology Projects(No.2012B031800293)the PhD Start-up program of Guangdong Province Natural Science Fund(No.S2012040008047)
文摘Background Whether pre-treatment with peroxisome proliferator activated receptor-γ （PPAR-γ） agonist has beneficial effect on myocardial ischemia / reperfusion （I/R） injury is not well established. In this study, we try to explore the cardioprotective effect of the pre-treatment with PPAR-γ agonist rosiglitazone （Ros） on the hearts suffering I/R injury. Methods Experimental I/R injury was induced by Langendorff heart reperfusion model and left anterior descending artery ligation in rats. Oxidative stress was evaluated by measuring lactate dehydrogenase （LDH）, nitric oxide synthase （NOS）, superoxide dismutase （SOD） and malonaldehyde （MDA）. Bcl-2 and Bax were detected by Western blotting and real-time PCR. Results Ros treatment significantly decreased SOD and inducible nitric oxide synthase and increased creatine kinase, LDH, MDA, and endothelial nitric oxide synthase in-vivo. Both in vitro and in-vivo, Ros treatment increased Bcl-2 level and decreased Bax level in a dose-dependent manner. In vitro, Ros treatment significantly increased SOD but lowered MDA and LDH in a dose-dependent manner. Conclusions Pre-treatment with PPARγ agonist Ros has beneficial effect on myocardial I/R injury by attenuating oxidative stress and inhibiting cardiomyocyte apoptosis.
