Development of an in vivo real-time measurement system of nitric oxide and superoxide and their clinical applications

一氧化氮和超氧化物体内实时测量系统的研制及其临床应用

• 批准号: 13555228
• 负责人: MOCHIZUKI Seiichi
• 金额: $ 6.46万
• 依托单位: Kawasaki College of Allied Health Professions
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13555228/
• 关键词: nitric oxide (NO); superoxide; sensor; catheter; endothelial function; superoxide dismutase (SOD); 酸化窒素(NO); スーパーオキサイド; 冠状静脈洞; センサー; in vivo計測

Development of a catheter-type NO sensor : First, we evaluated the basic performance of an in vivo NO sensor. Using a NO gas-saturated pure water, the sensor showed a sensitivity of about 580 pA/nM-NO. The sensor also demonstrated high selectivity to NO. When nitroglycerin was infused, plasma NO level in the abdominal aorta of an anesthetized rat increased to some nM level. Secondly, a proto-type catheter-type NO sensor was developed by encasing the in vivo NO sensor in a 4F catheter. The sensor was inserted into the thoracic aorta of an anesthetized dog. Plasma NO level increased transiently by acetylcholine (ACh) infusion. After inhibition of NO synthesis by L-NMMA, the ACh-induced increase in plasma NO level was significantly lower than that before L-NMMA. Finally, we have developed a catheter-type NO sensor for NO measurement in the proximal vessels. A soft tip was fixed at the edge of the detection tip. The sensor was inserted into the coronary sinus of an anesthetized dog. Intra-coronary infusion of ACh increased plasma NO level up to 5 nM. In conclusion, the newly developed catheter-type NO sensors demonstrated satisfying performance and would be applicable to clinical evaluation of endothelial function.Development of a superoxide sensor : A superoxide was prepared by fixing SOD on a Pt wire with some chemical modification. The sensor was located in a flow-cell-type measurement system. Isolated organs (heart, liver, and kidney) were loaded into the system, and superoxide level released from these organs could be measured successfully.

导管型NO传感器的开发：首先，我们评估了体内NO传感器的基本性能。使用NO气体饱和的纯水，传感器表现出约580 pA/nM-NO的灵敏度。传感器也表现出高选择性NO。当硝酸甘油注入，血浆NO水平在麻醉大鼠的腹主动脉增加到一些nM的水平。其次，通过将体内NO传感器封装在4F导管中来开发原型导管型NO传感器。将传感器插入麻醉犬的胸主动脉。乙酰胆碱（ACh）可使血浆NO水平一过性升高。用L-NMMA抑制NO合成后，ACh引起的血浆NO水平升高明显低于L-NMMA前。最后，我们开发了一种用于近端血管中NO测量的导管型NO传感器。将软尖端固定在检测尖端的边缘。将传感器插入麻醉犬的冠状窦。冠状动脉内输注ACh可使血浆NO水平升高至5 nM。总之，新开发的导管型NO传感器表现出令人满意的性能，并将适用于临床评价内皮功能。超氧化物传感器的开发：通过将SOD固定在Pt丝上并进行一些化学修饰来制备超氧化物。传感器位于流动池型测量系统中。将分离的器官（心脏、肝脏和肾脏）加载到系统中，并且可以成功地测量从这些器官释放的超氧化物水平。

项目成果

Mochizuki S, et al.: "Effect of dietary control on plasma nitrate level and estimation of basal systemic nitric oxide production rate in humans"Heart.Vessels. 15. 274-279 (2000)

Mochizuki S 等人：“饮食控制对血浆硝酸盐水平的影响以及人体基础全身一氧化氮生成率的估计”Heart.Vesses。

Seiichi Mochizuki, et al.: "Effect of dietary control on plasma nitrate level and estimation of basal systemic nitric oxide production rate in humans"Heart.Vessels. 15(6). 274-279 (2000)

Seiichi Mochizuki 等人：“饮食控制对血浆硝酸盐水平的影响以及人体基础全身一氧化氮生成率的估计”Heart.Vesses。

Seiichi Mochizuki, et al.: "Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release"Am.J.Physiol.Heart Circ.Physiol.. 285. H722-H726 (2003)

Seiichi Mochizuki等人：“透明质酸糖胺聚糖在剪切诱导的内皮源性一氧化氮释放中的作用”Am.J.Physiol.Heart Circ.Physiol..285.H722-H726(2003)

Seiichi Mochizuki: "Direct in situ evaluation of nitroglycerin-derived nitric oxide production in the canine and rat vascular walls at high temporal and spatial resolutions"Cardiovascular Engineering : An International Journal. 1・2. 85-91 (2001)

Seiichi Mochizuki：“在高时间和空间分辨率下对犬和大鼠血管壁中硝化甘油衍生的一氧化氮的产生进行直接原位评估”《心血管工程：国际期刊》85-91（2001）。

Miyasaka T, et al.: "Development of a contamination free 6 valve injector inline monitoring system for endotoxin measurement in dialysate"ASAIO J.. 48. 389-393 (2002)

Miyasaka T 等人：“开发用于透析液中内毒素测量的无污染 6 阀注射器在线监测系统”ASAIO J.. 48. 389-393 (2002)