Development of microdialysis probe for the kidney

肾脏微透析探针的研制

• 批准号: 04557010
• 负责人: ABE Youichi
• 金额: $ 5.31万
• 依托单位: Kagawa Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557010/
• 关键词: Micro-dialysis; Fiber-type probe; Adenosine; Inosine; Hypoxanthin; Kidney; Ischemia; Recirculation

The "bio-sampling" technique called microdialysis was originally developed by Ungerstedt and colleagues. The principle of this method is to extract metabolizes from the extracellular fluid(ECF) without removal of fluid from the tissue. The basic device is a thin (0.65 mm diameter) double lumen probe with a seim-permeable polycarbonate membrane at the tip. The probe is perfused with an isotonic saline. Small molecules cross the probe membrane by simple difusion along a concetration gradient between the perfusate and the ECF.The dialysate microsample content of various metabolizes is measured by sensitive analytical techniques including HPLC.Thus, microdialysis can be used for temporal studies of regional changes in the ECF content of various metabolizes. The method was originally designed for studies in brain tissue. However, the diameter of the microdialysis probe is 0.65 mm. This size is relatively large for the application to the kidney which is perfused at high blood flow rate. Moreover, since the kidney moves in synchronicity with the respiration, the fixation of probe is difficult. In addition, to observe the rapid responses to various stimuli high dialysis efficiency will be required for probe. Thus, in order to satisfy the above points, we have tried to develop a new microdialysis probe for the kidney. The diameter of the new probe is only 0.2 mm and the dialysis efficiency is 5 - 10 times greater than the commercial probe. Using this newly developed probe we have examined the intrarenal adenosine metabolism during ischemia and recirculation. Adenosine concentration(conc.) at basal condition was around 100 nM.Ischemia increased the adenosine conc.about 2 times. However, after the inhibition of adenosine deaminase with EHNA the adenosine conc.was increased more than 50 - 100 times during ischemia. On the other hand, adenosine conc.after the inhibition of adenosine kinase with iodotubercidine increased only 3 - 4 times. Thus, the adenosine released from the ce

这种名为微透析的“生物采样”技术最初是由昂格斯泰特和他的同事开发的。这种方法的原理是从细胞外液(ECF)中提取代谢产物，而不从组织中去除液体。基本装置是一个薄的(直径0.65 mm)双腔探头，尖端有一层可渗透的聚碳酸酯薄膜。探头中注入了等渗盐水。小分子沿着灌流液和ECF之间的浓度梯度通过简单的DiFusion穿过探针膜。各种代谢物的透析液微量样品含量可以通过包括HPLC在内的灵敏分析技术来测量。因此，微透析可以用于研究各种代谢物ECF含量的区域变化的时间变化。该方法最初是为研究脑组织而设计的。然而，微透析探头的直径为0.65 mm。对于以高血流速度灌流的肾脏来说，这个大小相对较大。此外，由于肾脏的运动与呼吸同步，探头的固定也很困难。此外，为了观察对各种刺激的快速反应，探头需要有较高的透析效率。因此，为了满足上述要求，我们尝试开发了一种新型的肾脏微透析探头。新型探头直径仅0.2 mm，透析效率是市售探头的5-10倍。使用这一新开发的探针，我们已经检测了缺血和再循环期间肾内腺苷的代谢。腺苷浓度(续)在基础状态下约100 nM，缺血使腺苷浓度增加约2倍。然而，用eHNA抑制腺苷脱氨酶后，腺苷浓度在缺血时升高了50-100倍以上。而在腺苷激酶被碘化结核抑制后，腺苷浓度仅增加3-4倍。因此，腺苷从CE中释放出来

项目成果

T.Tamaki, K.Hasui, Y.Aki, S.Kimura and Y.Abe: "Effects of NG-nitro-arginine on isolated rabbit afferent arterioles." Jpn.J.Pharmacol.62. 231-237 (1993)

T.Tamaki、K.Hasui、Y.Aki、S.Kimura 和 Y.Abe：“NG-硝基-精氨酸对离体兔传入小动脉的影响。”

Tetuo Shoji: "Regional hemodynamic effects of betaxolol,a new selective β_1-blocker,and atenolol in conscious spontaneously hypertensive rats" Japanese Journal of Pharmacology. 60. 253-259 (1992)

Tetuo Shoji：“倍他洛尔（一种新型选择性 β_1 阻滞剂）和阿替洛尔对清醒自发性高血压大鼠的区域血流动力学影响”《日本药理学杂志》60. 253-259 (1992)。

Hideyasu Kiyomoto: "Effect of L-N^<-G> nitro-arginine,inhibitor of nitric oxide synthesis,on autoregulation of renal blood flow in dogs" Japanese Journal of Pharmacology. 58. 147-155 (1992)

Hideyasu Kiyomoto：“一氧化氮合成抑制剂 L-N^<-G> 硝基精氨酸对狗肾血流自动调节的影响”《日本药理学杂志》。

Akira Nishiyama: "Effects of semotiadil fumarate(SD-3211)on renal hemodynamics and function in dogs" Eur.J.Pharmacol.218. 311-317 (1992)

Akira Nishiyama：“富马酸赛替地尔 (SD-3211) 对狗肾血流动力学和功能的影响”Eur.J.Pharmacol.218。

Y.Aki, T.Tamaki, H.Kiyomoto, H.He, H.Iwao and Y.Abe: "Nitric oxide may participate in V2 vasopressin-receptor-mediated renal vasodilation" J.Cardiovasc.Pharmacol. 23. 331-336 (1994)

Y.Aki、T.Tamaki、H.Kiyomoto、H.He、H.Iwao 和 Y.Abe：“一氧化氮可能参与 V2 加压素受体介导的肾血管舒张” J.Cardiovasc.Pharmacol。