Apocynin和allopurinol对运动上调自发性高血压大鼠肾脏一氧化氮合成酶表达的影响

Hypertension is the most common chronic disease. Nitric oxide　(NO),　which is produced by nitric oxide synthase　(NOS) has numerous physiological roles　including vasodilator and diuretic actions, and plays an important role in the regulation of cardiovascular and renal functions. The most relevant aources of ROS,with respect to hypertension appear to be NADPH oxidase and xanthine oxidase.Oxidative stress and reactive oxygen species (ROS) are elevated, leading to NO-mediated vasodilatory responses were impaired in SHR. In the previous studies of ours, the exercise training lowered the ROS and increased NOS expression and the bioactivity of NO in the aorta and kidney of SHR. Thus, Exercise training shows antihypertensive effects and renal protection. At present, several mechanisms have been clarified to regulate the NOS expression by exercise in cardiovascular system of a hypertensive state. However, the mechanisms of upregulated renal NOS expression and renal-protective effects of exercise are not entirely understood. To clarify the mechanism of antihypertensive and renal-protective effect of the exercise, the present study tested the impacts of the apocynin (the inhibitor of NADPH oxidase)and allopurinol(the inhibitor of xanthine oxidase) on the exercise training-upregulated NOS expression in the kidney of SHR. This study is one of the few molecular biological research in exercise training-upregulated renal NOS expression of a hypertensive state. We hope that exercise could be extended in clinic rehabilitation of cardiovascular, and be a novel therapeutic approach for preventing the development of renal dysfunction in hypertensive patients.

高血压是最常见的慢性病。NO具有扩张血管，利尿等的生理活性，在改善循环系统机能，调节肾机能的过程中发挥着重要作用。与高血压发病相关的高ROS水平，主要由NADPH oxidase和Xanthine oxidase氧化应激介导产生。SHR体内明显升高的ROS水平，导致体内NO生物活性的下降。我们先前的研究发现，运动可以降低SHR心血管系统和肾脏的ROS水平，上调NOS的表达，提高NO生物活性。目前运动上调心血管系统NOS表达的机制基本明晰，但运动上调肾脏NOS表达的机制还不甚清楚。因此，本研究旨在通过研究"NADPH oxidase抑制剂"apocynin和"Xanthine oxidase抑制剂"allopurinol对运动上调的SHR肾脏NOS表达的影响，探究运动上调SHR肾脏NOS表达的分子生物学机制。希望以此，为运动疗法在心肾康复临床实际工作中的应用与推广，提供必要的理论支持。

高血压是最常见的慢性病。一氧化氮具有扩张血管，利尿等的生理活性，在改善循环系统机能，调节肾机能的过程中发挥着重要作用。自发性高血压大鼠体内明显升高的氧化应激和活性氧的水平，导致体内NO生物活性的下降。我们先前的研究发现，运动可以降低SHR心血管系统和肾脏的氧化应激，上调一氧化氮合成酶的表达，提高NO生物活性；从而延缓高血压进展，改善肾功能。目前关于运动上调心血管NOS表达的机制被广泛认知；但对运动上调肾脏NOS表达的机制还不甚清楚。因此，本研究旨在通过研究“NADPH Oxidase抑制剂”Apoynin和“Xanthion Oxidase抑制剂”allopurinol对运动上调的SHR肾脏NOS表达的影响，探究运动上调SHR肾脏NOS表达的分子生物学机制。. 我们对正常血压的WKY大鼠和自发性高血压大鼠SHR进行了对比研究。WKY或SHR分别随机分为对照组，运动组，药物Apocynin组，药物Allopurinol组，药物Apocynin+Allopurinol组，运动+药物Apocynin组，运动+药物Allopurinol组，运动+药物Apocynin+Allopurinol组。分别对各组进行了血常规和尿常规检测，肾的NADPH oxidase活性测定，血浆和尿过氧化氢测定，血浆和尿NOx测定，肾NOS的测定。. 运动显著提高WKY的血浆及尿NOx、过氧化氢含量，以及肾脏的eNOS和nNOS表达；药物Apocynin去除了运动的效果，但药物Allopurinol对运动的效果没有改变。运动显著提高SHR的血浆及尿NOx、过氧化氢含量，以及肾脏的eNOS和nNOS表达；药物Apocynin削弱了运动的效果，但没有达到单独药物Apocynin组水平；药物Apocynin+Allopurinol完全去除了运动的效果。. 药物Apocynin对运动上调WKY和SHR的肾NOS效果不尽相同，但药物Apocynin+Allopurinol对运动上调WKY和SHR肾NOS效果完全一致。说明，运动改善高血压状态的的高氧化应激，和肾脏保护作用，不仅通过有NADPH oxidase途径，还有Xanthion Oxidase的途径。因此，运动疗法作为一种新型的治疗手段，在心肾等疾患康复治疗中具有多途径、多靶点的复合效果。