国际病理科学与临床杂志2017，Vol.37Issue(11)：2310-2316,7.DOI:10.3978/j.issn.2095-6959.2017.11.005
PAK1-nNOS-NO信号通路在有氧运动减轻压力负荷小鼠心肌肥厚中的作用及其机制
Aerobic exercise attenuates pressure overload-induced cardiac hypertrophy through regulating PAKI-nNOS-NO signalling in mice
摘要
Abstract
Objective:To clarify the role of PAK1 involved in the cardioprotective effect of aerobic exercise and the precise mechanism.Methods:TAC was used to induce cardiac hypertrophy via pressure overload.Aerobic exercise was carried out in the form of swimming.C57BL6/J mice were arbitrarily divided into the following groups:a sham-operated control group (SHAM),a sham-operated control + Exercise training group (SHAM+E),a TAC group (TAC),a TAC + Exercise training group (TAC+E),and a TAC + Exercise training group + IPA-3 group (TAC+E+I).Heart weight to body weight ratio and the changes of cardiac geometry were performed to reveal the extent of cardiac hypertrophy.wheat germ agglutinin staining was performed to reveal the extent of myocyte hypertrophy;cardiac NO production,MDA levels and SOD activity were determined using ELASA kit.Western blotting was performed to investigate p-PAK1,eNOS,p-eNOS Ser114,nNOS,p-nNOS Ser1412 protein expression.Results:With time after the surgery,the HW/BW,LVM,LVPW,IVSS,the myocyte cross-sectional area and MDA were increased,the levels of SOD,p-PAK1 expression and the NO metabolite concentration were decreased in the TAC group compared with the SHAM group.Exercise training reduced HW/BW and LVM after TAC,augmented the SOD level and decreased the MDA level,and augmented p-PAK1 and NO production.IPA-3,a PAK1 inhibitor,partly abolished the effect of exercise training.More,Western blot analysis showed eNOS and nNOS protein was improved,p-nNOS Ser1412 and p-eNOS Ser114 were decreased in the TAC group compared with the SHAM group.Meanwhile,exercise training significantly increased total nNOS,p-nNOS Ser1412 and p-eNOS Ser114 expression in the TAC + E group compared with the TAC group.In addition,IPA-3 decreased the expression of both total nNOS,p-nNOS Ser1412,while the levels of eNOS and p-eNOS Ser114 was not changed in the TAC+E+I group compared with the TAC+E group.Conclusion:Aerobic exercise attenuates pressure overload-induced cardiac hypertrophy through regulating PAK1-nNOS-NO signalling in mice.关键词
心肌肥厚/有氧运动/一氧化氮/PAK1Key words
cardiac hypertrophy/aerobic exercise/NO/PAK1引用本文复制引用
冯品,楚轶,曾迪,张薇..PAK1-nNOS-NO信号通路在有氧运动减轻压力负荷小鼠心肌肥厚中的作用及其机制[J].国际病理科学与临床杂志,2017,37(11):2310-2316,7.基金项目
国家自然科学基金(81470537,31400832).This work was supported by National Natural Science Foundation of China(81470537,31400832). （81470537,31400832）
