羟基酪醇对过度训练大鼠心肌线粒体动力学蛋白及自噬水平的影响

摘要

This study evaluated the changes of mitochondrial respiratory functions,observe the mitochondrial dynamics and autophagy related proteins alterations,explored HT - induced favora-ble protections for myocardium in excessive training animals. Methods:80 Sprague dawley rats were subjected and divided into four groups:sedentary group( CON),sedentary + HT group( CON +HT),excessive exercise training group(ET)and ET + HT group. Administration regimen:25mg /kg / d. Training from Monday to Friday every week for eight weeks. Oxygen consumption was used for evaluating the mitochondrial respiratory functions. Westerblot was used to determine the mito-chondrial biogenesis(Pgc - 1α),complexes protein expressions,mitochondrial dynamics(fusion:Mfn1 / 2,Opa1;fission:Drp1)and autophagy associated proteins(atg5,beclin - 1and lc3 - B). Re-sults:ET showed significant decrease on mitochondrial respiratory control rate(RCR)and value of P/ O,downregulated PGC - 1α and complex I,IV and V levels. ET also revealed to induce mito-chondrial dynamics pathological remodelling(increased fission[Drp1]and decreased fusion[Mf2 and Opa1])and elevated autophagy level(Atg5,Beclin - 1). HT treatment efficiently increased P/O,complex I and V levels,which were indicated to the increased protein levels of Pgc - 1α,Mfn2 and Opa1,but decreased Drp1,Atg5 and Lc3 - B. Conclusion:These results demonstrated that ET -induced myocardial mitochondrial dysfunctions may be mediated via the downregulation of mitochon-drial biogenesis,dynamic proteins and upregulation of autophagy. HT may normalize the mitochon-drial dynamic remodeling and decrease autophagy,thereby improve the mitochondrial functional per-formances.%目的：研究检测 ET 后心肌线粒体功能，观察羟基酪醇 HT 对线粒体功的保护效应，并通过关注动力学及自噬蛋白变化，探讨 HT 保护机制。方法：80只 SD 大鼠随机分成4组，即：正常对照组（CON），正常加羟基酪醇组（CON + HT），过度训练组（ET）及训练加羟基酪醇组（ET + HT）。灌胃给药，剂量为25 mg / kg / d，每周训练时间为周一至周六，共8周，氧耗法测定线粒体呼吸功能。Westerblot 法检测线粒体生物合成（PGC -1α），复合物（I，II，III，IV，V），动力学（融合：Mfn1/2，OPA1；裂解：Drp1）及自噬相关蛋白（Atg5，Beclin -1及 Lc3- B）。结果：ET 可显著性降低线粒体呼吸控制率（RCR）及磷氧比值（P/ O），下调 PGC -1α及复合物 I，IV， V 表达，增加线粒体裂解（Drp1），降低融合（Mfn2，Opa1）。相对地，HT 可有效提高线粒体 P/O 及复合物 I，V 表达水平；促进生物合成（ Pgc -1α），提高融合（ Mfn2，Opa1），降低裂解（Drp1）和自噬（Atg5，Lc3- B）。结论：ET 造成的心肌线粒体功能异常与动力学蛋白及自噬水平变化相关。HT 对上述病理性变化的抑制作用可能是其发挥保护作用的重要机制。