基于“风为百病之长”探讨祛风养心法调节Sirt3改善细胞自噬抑制高血压心肌肥厚的机制

Hypertensive myocardium hypertrophy significantly increases the incidence of heart failure, which is an urgent problem to be solved. Studies have proved that abnormal accumulation of proteins caused by autophagy dysfunction is the important pathomechanism for hypertensive myocardial hypertrophy, and Sirt3 is a key molecule in regulating the autophagy pathway. Based on the theory of "wind is the leading factor in causing diseases" and clincal researches，we proved the method of dispelling wind is an important treatment for heart diseases. The basic research and pre-experiments of our research cleared that the method of Qufeng Yangxin could improve ventricular remodeling in patients with atrial fibrillation, inhibit hypertensive model rats myocardium hypertrophy induced by isoproterenol , and promote the down-regulated Sirt3 protein expression at the same time. Combined with the existing studies on the intervention of autophagy by Yiqi Huoxue method , our research group proposed the hypothesis that "the key mechanism of Qufeng Yangxin method in inhibiting hypertrophy of hypertensive myocardium is closely related to the regulation of Sirt3 to improve the autophagy pathway".This trails use SHR rats and H9c2 cardiomyocyte as experimental objects, and gene inhibition and overexpression techniques were applied to further investigate the effect of Qufeng Yangxin therapy on Sirt3 expression and the regulation mechanism of Sirt3 on the autophagy pathway (AMPK/ m-Tor) in order to clarify the consistency of Sirt3 regulating autophagy with "wind is the leading factor in causing diseases".and to provide a scientific basis for Qufeng Yangxin method curing Hypertensive myocardium hypertrophy.

高血压心肌肥厚显著增加心力衰竭的发生率，是亟待解决的问题。已证实细胞自噬失调导致蛋白异常积累是高血压心肌肥厚重要病理机制，在调节细胞自噬通路上Sirt3是关键分子。课题组根据“风为百病之长”中医理论结合前期临床研究证明祛风法是治疗心系疾病重要治法，并证实祛风养心法可改善房颤患者心室重塑，抑制异丙肾上腺素高血压模型大鼠心肌肥厚，促进Sirt3蛋白表达，结合益气活血法干预细胞自噬的现有研究，课题组提出“祛风养心法抑制高血压心肌肥厚的关键环节与调节Sirt3改善细胞自噬通路密切相关”的假说。本课题拟以SHR大鼠及H9c2心肌细胞为实验对象，应用基因抑制和过表达技术深入探讨祛风养心法对Sirt3的表达影响，以及Sirt3对细胞自噬通路（AMPK/m-TOR）调控机制，以期阐明Sirt3调节细胞自噬与中医理论“风为百病之长”内涵的一致性，为祛风养心法治疗高血压心肌肥厚奠定科学基础。

高血压心肌肥厚显著增加心力衰竭的发生率，是亟待解决的问题。已证实细胞自噬失调导致蛋白异常积累是高血压心肌肥厚重要病理机制，在调节细胞自噬通路上Sirt3是关键分子。课题组祛风养心方可以调节Sirt3蛋白表达，因此课提出祛风养心法抑制高血压心肌肥厚的关键环节与调节Sirt3改善细胞自噬通路密切相关”的假说。本课题通过以SHR大鼠及H9c2心肌细胞为实验对象，应用慢病毒转染技术深入探讨祛风养心法对Sirt3 的表达影响，以及Sirt3对细胞自噬通路（AMPK/m-TOR）调控机制。通过实验得出结果：1.体内实验得出祛风养心法可以抑制SHR大鼠高血压心肌肥厚，改善心肌结构紊乱，降低心肌细胞面积，改善心室重塑，降低心肌肥厚及自噬代表基因的表达，提高Sirt3蛋白表达水平；2.体外实验得出祛风养心法可以抑制AngII诱导H9c2细胞肥大，降低细胞肥大和细胞自噬标志基因蛋白的表达，提高Sirt3的表达同时提高P-AMPK，降低P-mTOR，这种改善作用在慢病毒转染抑制Sirt3表达心肌细胞组中被逆转。.本实验结果表明：祛风养心法可以通过促进Sirt3表达调整AMPK-mTOR通路，改善自噬，通畅自噬流，抑制高血压导致的心肌肥厚，延缓病情进展。 本研究扩充中医理论“风为百病之长”内涵，为祛风养心法治疗高血压心肌肥厚奠定科学基础，为复方中药的开发提供实验依据。

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