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缺血预处理对麻醉犬缺血后肾功能的保护作用:腺苷和腺嘌呤核苷酸的作用。

Ischemic preconditioning protects post-ischemic renal function in anesthetized dogs: role of adenosine and adenine nucleotides.

作者信息

Li Fan-Zhu, Kimura Shoji, Nishiyama Akira, Rahman Matlubur, Zhang Guo-Xing, Abe Youichi

机构信息

Department of Pharmaceutics, Zhejiang College of Traditional Chinese Medicine, Hangzhou 310053, China.

出版信息

Acta Pharmacol Sin. 2005 Jul;26(7):851-9. doi: 10.1111/j.1745-7254.2005.00109.x.

DOI:10.1111/j.1745-7254.2005.00109.x
PMID:15960893
Abstract

AIM

To investigate the effects of renal ischemic preconditioning (IPC) on both renal hemodynamics and the renal interstitial concentrations of adenosine and adenine nucleotides induced by ischemia-reperfusion injury.

METHODS

Renal hemodynamics responses to ischemia-reperfusion injury in mongrel dog models were determined with or without multiple brief renal ischemic preconditioning treatments, as well as the adenosine A1 receptor antagonist (KW-3902), respectively. The renal interstitial concentrations of adenosine and adenine nucleotides in response to ischemia-reperfusion injury, either following 1-3 cycles of IPC or not, were measured simultaneously using microdialysis sampling technology.

RESULTS

One 10-min IPC, adenosine A1 receptor antagonist (KW-3902) also shortened the recovery time of renal blood flow (RBF) and urine flow (UF), as well as mean blood pressure (BP). Advanced renal IPC attenuated the increment of adenosine and adenine nucleotides, as well as recovery time during the 60-min reperfusion which followed the 60-min renal ischemia. All of these recovery times were dependent on the cycles of 10-min IPC. The renal interstitial concentrations of adenosine and adenine nucleotides increased and decreased during renal ischemia and reperfusion, respectively.

CONCLUSION

A significant relativity in dog models exists between the cycles of 10-min renal IPC and the recovery time of BP, UF, and RBF during the 60-min renal reperfusion following 60-min renal ischemia, respectively. Renal IPC can protect against ischemia-reperfusion injury and the predominant effect of endogenous adenosine induced by prolonged renal ischemia; renal adenosine A1 receptor activation during the renal ischemia-reperfusion injury is detrimental to renal function.

摘要

目的

研究肾缺血预处理(IPC)对肾血流动力学以及缺血再灌注损伤诱导的肾间质中腺苷和腺嘌呤核苷酸浓度的影响。

方法

分别在有或无多次短暂肾缺血预处理以及使用腺苷A1受体拮抗剂(KW - 3902)的情况下,测定杂种犬模型中肾血流动力学对缺血再灌注损伤的反应。使用微透析采样技术同时测量在进行1 - 3个肾缺血预处理循环或未进行预处理的情况下,肾间质中腺苷和腺嘌呤核苷酸对缺血再灌注损伤的反应浓度。

结果

一次10分钟的肾缺血预处理,腺苷A1受体拮抗剂(KW - 3902)也缩短了肾血流量(RBF)、尿流量(UF)以及平均血压(BP)的恢复时间。预先进行多次肾缺血预处理可减轻腺苷和腺嘌呤核苷酸的增加以及在60分钟肾缺血后的60分钟再灌注期间的恢复时间。所有这些恢复时间均取决于10分钟肾缺血预处理的循环次数。在肾缺血和再灌注期间,肾间质中腺苷和腺嘌呤核苷酸的浓度分别升高和降低。

结论

在犬模型中,10分钟肾缺血预处理的循环次数与60分钟肾缺血后60分钟肾再灌注期间的血压、尿流量和肾血流量的恢复时间之间存在显著相关性。肾缺血预处理可预防缺血再灌注损伤以及长期肾缺血诱导的内源性腺苷的主要作用;肾缺血再灌注损伤期间肾腺苷A1受体的激活对肾功能有害。

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