中国病理生理杂志2024，Vol.40Issue(2)：193-203,11.DOI:10.3969/j.issn.1000-4718.2024.02.001
亚精胺通过改善心脏线粒体能量代谢缓解压力超负荷小鼠心力衰竭
Spermidine alleviates pressure overload-induced heart failure in mice via improving cardiac mitochondrial energy metabolism
摘要
Abstract
AIM:To investigate the effect of spermidine(SPD)on pressure overload-induced cardiac hyper-trophy and heart failure model in mice and its underlying mechanisms.METHODS:(1)Eight-week-old male C57BL/6J mice were randomly divided into 4 groups:sham group,sham+SPD group,transverse aortic constriction(TAC)group,and TAC+SPD group.After TAC,the mice in sham+SPD group and TAC+SPD group were fed with 3 mmol/L SPD via drinking water,and the mice in other groups were fed with normal water.Western blot was used to detect the protein ex-pression levels of silent information regulator 6(SIRT6),peroxisome proliferator-activated receptor γ coactivator-1(PGC-1)and mitofusin 2(MFN2).Adult mouse cardiomyocytes were isolated to detect cell length and width.Wheat germ agglu-tinin staining was used to detect the cardiac cell size.Masson staining was used to detect the extent of fibrosis.Echocar-diography was used to detect cardiac function and myocardial hypertrophy.Transmission electron microscopy was used to analyze mitochondrial morphology.Oxygraph-2k high-resolution respirometer was used to detect cardiac mitochondrial oxy-gen consumption.(2)In vitro,primary rat ventricular cardiomyocytes were cultured and treated with angiotensin II(Ang II;1 μmol/L)to construct a hypertrophy model of cardiomyocytes.These cardiomyocytes were divided into control(Con)group,Con+SPD(1 mmol/L)group,Ang II group,Ang II+SPD group and Ang II+SPD+SIRT6 siRNA(siSIRT6)group.Confocal microscopy was used to detect cardiomyocytes area and mitochondrial.RESULTS:(1)Compared with sham group,cardiac function of the mice in TAC group was significantly decreased(P＜0.05),the degree of myocardial hyper-trophy was significantly increased(P＜0.05),and the expression levels of SIRT6,PGC-1 and MFN2 in the myocardial tis-sue were significantly decreased(P＜0.05).Compared with TAC group,the expression levels of SIRT6,PGC-1 and MFN2 in mouse myocardial tissues of TAC+SPD group were significantly increased(P＜0.05),pathological myocardial hy-pertrophy was reduced(P＜0.05),the numbers of mitochondria and mitochondrial cristae were increased(P＜0.05),mito-chondrial function was restored(P＜0.05),myocardial fibrosis was alleviated(P＜0.05),and cardiac function was im-proved(P＜0.05).(2)In vitro,compared with Con group,the expression levels of SIRT6,PGC-1 and MFN2 in cardio-myocytes of Ang II group were decreased(P＜0.05),and the degree of cardiomyocyte hypertrophy was significantly in-creased(P＜0.05).Treatment with SPD increased the expression levels of SIRT6,PGC-1 and MFN2 in cardiomyocytes of Ang II group(P＜0.05),reversed myocardial hypertrophy and improved mitochondrial dynamics(P＜0.05).Compared with Ang II group,the expression levels of SIRT6,PGC-1 and MFN2 in Ang II+SPD+siSIRT6 group showed no significant changes,and the degree of cardiomyocyte hypertrophy and mitochondrial dynamics also had no statistically significant changes.CONCLUSION:Spermidine promotes the expression of SIRT6,PGC-1 and MFN2,thus improving mitochon-drial function,reducing myocardial hypertrophy and alleviating heart failure in mice with pressure overload.关键词
亚精胺/心肌肥大/心力衰竭/线粒体能量代谢/沉默信息调节因子6/过氧化物酶体增殖物激活受体γ辅激活因子1/线粒体融合蛋白2Key words
spermidine/cardiac hypertrophy/heart failure/mitochondrial energy metabolism/silent infor-mation regulator 6/eroxisome proliferator-activated receptor γ coactivator-1/mitofusin 2分类
医药卫生引用本文复制引用
张晓亮,赵晓玲,耿静,胡朗,李妍..亚精胺通过改善心脏线粒体能量代谢缓解压力超负荷小鼠心力衰竭[J].中国病理生理杂志,2024,40(2):193-203,11.基金项目
国家自然科学基金资助项目(No.81770369 （）
No.82300443) （）
