运动训练对高血压性心脏病的疗效及作用机制的研究

Hypertension is a prevalent syndrome which is one of the major risk factors for hypertensive heart diseases. Neuronal nitric oxide synthase (nNOS) has been implicated to be one of the major influences of cardiac contractile function. All current treatment guidelines emphasise the role of nonpharmacological interventions, including exercise training, in the treatment of hypertension. It is known that nNOS is up-regulated in the myocardium following exercise training and protect the cardiac function. However, its subcellular localization, molecular mechanism and their interplays in regulating contractile function is not clear. Therefore, we aim to test the protective effect of exercise and functional regulation by nNOS of LV myocyte contraction in hypertensive rats. This study is the first attempt to suggest that exercise promotes the expression and activity of nNOS, which is responsible for the regulating contractile function and treatment of hypertensive heart disease. Furthermore, this research will provide insights into key signalling pathways that may become the focus of novel strategies for the treatment and prevention of Hypertension and cardiovascular disease.

高血压是最常见的慢性病, 高血压引起的心脏改变称高血压性心脏病。我们的前期研究中发现神经型一氧化氮合酶（nNOS）是高血压心肌中的保护因子之一。目前国际高血压治疗指南强调运动疗法。运动训练可上调心肌细胞内nNOS表达并改善心功能。然而上调的nNOS在细胞内定位及分子作用机制与改善心功能的相互关系尚不明确。本课题拟通过建立动物模型，探讨运动训练对高血压模型中心功能的影响；比较细胞内nNOS的变化，揭示nNOS对心功能的作用及其分子机制。本研究结果将首次阐述运动训练通过上调nNOS信号途径，控制高血压性心脏病的发生发展,为运动训练在高血压及相关疾病中的疗效，提供坚实的理论依据，具有重要的临床意义和广泛的应用前景。

运动训练可通过神经型一氧化氮合酶（nNOS）的蛋白质调节来控制和预防高血压性心脏病的发生和发展，其nNOS的作用机制为cTnI23/24和cMyBP-C蛋白的磷酸化，调节肌丝钙敏感性，从而保护心脏收缩功能；抑制钙离子释放通道的功能，调节心肌肌浆网（SR）对钙离子的摄取和释放能力，并可以抑制心肌SR的钙超载；改变nNOS的细胞内分布来调节心功能。本研究是通过建立运动、高血压与高血压运动模型，探讨运动训练对高血压动物模型中心功能的影响；比较细胞内nNOS的变化；揭示nNOS对心功能的作用及其分子机制，阐明运动训练通过nNOS来改善心功能的分子机制，为高血压性心脏病的防病、控病和治病提供新的理论基础，具有重要的临床意义和广泛的应用前景。项目资助发表SCI论文1篇，国内期刊论文11篇，获得实用新型专利1项，荣获吉林省自然科学学术成果奖、吉林省科学技术奖、第十四届长城青年医师奖，培养硕士研究生4名。