目的:研究远隔缺血预处理(remote ischemic preconditioning, RIPC)促进压力负荷性心肌肥厚(pressure-overload myocardial hypertrophy, POMH)术后逆重构的作用及机制。方法:建立H9C2心肌细胞模型,分为正常对照组(Sham)、POMH组、RIPC组,通过定量PCR与Western blot检测各组内细胞凋亡以及线粒体自噬相关蛋白的表达水平。结果:PCR结果显示,给予RIPC处理后能够明显抑制POMH中细胞凋亡率的升高;Western blot结果显示RIPC能够通过上调线粒体自噬相关蛋白表达达到促进POMH术后逆重构的作用。结论:RIPC能够促进POMH术后逆重构,其机制与线粒体自噬相关。
Objective: To investigate the role and mechanisms of remote ischemic preconditioning (RIPC) in promoting the reverse remodeling after pressure-overload myocardial hypertrophy (POMH). Methods: H9C2 myocardial cell model was established. The rats were divided into the normal control group (Sham), POMH group and RIPC group. The apoptosis and expression levels of mitochondrial autophagy-related proteins in each group were detected by quantitative PCR and Western blot. Results: PCR results showed that RIPC could significantly inhibit the increasing rate of apoptosis in the POMH group. Western blot results showed that RIPC could promote reverse remodeling after POMH surgery by up-regulating the expression levels of mitochondrial autophagy-related proteins. Conclusion: RIPC could promote reverse remodeling after POMH surgery and its mechanism was related to mitochondrial autophagy.
[1] Joseph J,Naqvi SY,Giri J,et al.Aortic stenosis:pathophysiology,diagnosis,and therapy[J].Am J Med,2017,130(3):253-263.
[2] Toyama EQ,Herzig S,Courchet J,et al.Metabolism.AMP-activated protein kinase mediates mitochondrial fission in response to energy stress[J].Science,2016,351(6270):275-281.
[3] Wu Q,Luo CL,Tao LY.Dynamin-related protein1(Drp1) mediating mitophagy contributes to the pathophysiology of nervous system diseases and brain injury[J].Histol Histopathol,2017,32(6):551-559.
[4] Yamashita SI,Jin X,Furukawa K,et al.Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1during mitophagy[J].J Cell Biol,2016,215(5):649-665.
[5] Polletta L,Vernucci E,Carnevale I,et al.SIRT5regulation of ammonia-induced autophagy and mitophagy[J].Autophagy,2015,11(2):253-270.
[6] Zhao WY,Zhang L,Sui MX,et al.Protective effects of sirtuin3in a murine model of sepsis-induced acute kidney injury[J].Sci Rep,2016,6:33201.
[7] Szeto HH,Liu S,Soong Y,et al.Mitochondria protection after acute ischemia prevents prolonged upregulation of IL-1beta and IL-18and arrests CKD[J].J Am Soc Nephrol,2017,28(5):1437-1449.
[8] Liu TQ,Fang Y,Liu SP,et al.Limb ischemic preconditioning protects against contrast-induced acute kidney injury in rats via phosphorylation of GSK-3beta[J].Free Radic Biol Med,2015,81:170-182.
[9] Zuo Z,Jing K,Wu H,et al.Mechanisms and functions of mitophagy and potential roles in renal disease[J].Front Physiol,2020,11:935.
[10] Jabbari H,Roushandeh AM,Rostami MK,et al.Mitochondrial transplantation ameliorates ischemia/reperfusion-induced kidney injury in rat[J].Biochim Biophys Acta Mol Basis Dis,2020,1866(8):165809.
[11] Heinzel FR,Hohendanner F,Jin G,et al.Myocardial hypertrophy and its role in heart failure with preserved ejection fraction[J].J Appl Physiol(1985),2015,119(10):1233-1242.
[12] Bharath LP,Agrawal M,McCambridge G,et al.Metformin enhances autophagy and normalizes mitochondrial function to alleviate aging-associated inflammation[J].Cell Metab,2020,32(1):44-55.
[13] Onishi M,Yamano K,Sato M,et al.Molecular mechanisms and physiological functions of mitophagy[J].EMBO J,2021,40(3):e104705.
[14] Wang K,Ojamaa K,Samuels A,et al.BNP as a new biomarker of cardiac thyroid hormone function[J].Front Physiol,2020,11:729.
[15] Semenov AG,Feygina EE.Standardization of BNP and NT-proBNP immunoassays in light of the diverse and complex nature of circulating BNP-related peptides[J].Adv Clin Chem,2018,85:1-30.
[16] Błogowski W,Dołegowska B,Sałata D,et al.Clinical analysis of perioperative complement activity during ischemia/reperfusion injury following renal transplantation[J].Clin J Am Soc Nephrol,2012,7(11):1843-51.
[17] Runwal G,Stamatakou E,Siddiqi FH,et al.LC3-positive structures are prominent in autophagy-deficient cells[J].Sci Rep,2019,9(1):10147.
[18] 张新会,罗文龙,裴汉军.3-MA对缺氧/复氧心肌细胞自噬及凋亡的影响[J].包头医学院学报,2020,36(6):47-51.
[19] Tran S,Fairlie WD,Lee EF.BECLIN1:protein structure,function and regulation[J].Cells,2021,10(6):1522.
