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[激肽释放酶-激肽系统的生物学调节:对激肽原缺陷大鼠品系的研究]

[Biological regulation by the kallikrein-kinin system: a study with a kininogen-deficient rat strain].

作者信息

Oh-Ishi S

机构信息

Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.

出版信息

Nihon Yakurigaku Zasshi. 1993 Apr;101(4):209-18. doi: 10.1254/fpj.101.4_209.

Abstract

It is well known that the kallikrein-kinin system expresses potent biological activities through its final product, bradykinin. However, bradykinin has an extremely short half life in biological fluids, so that it is difficult to quantitate the amount of bradykinin released in relevant pathological samples. Therefore investigators have attempted to prove its involvement or importance by measuring the precursor proteins, such as prekallikrein, kininogens, and glandular kallikreins. In this review, I would like to focus the discussion on a study of the kallikrein-kinin system in B/N Katholiek rats, a strain that has a congenital deficiency in plasma high molecular weight and low molecular weight kininogens. When experimental inflammation induced in the mutant deficient rats are compared to that induced in the normal rats (B/N-Kitasato), there was a significant difference; i.e., the deficient rats showed less swelling in the carrageenin-induced paw edema and less exudate accumulation in carrageenin-induced rat pleurisy. These results indicate that bradykinin may be released from kininogens and it may cause exudate formation in above inflammation. Furthermore, when experimental hypertension was induced by DOCA-salt loading, the blood pressure of the deficient rats rose faster than that of the normal rats. From the above findings, it is concluded that the plasma kallikrein-kinin system could be an important regulatory system in body defense mechanisms such as inflammation and blood pressure control.

摘要

众所周知,激肽释放酶-激肽系统通过其终产物缓激肽发挥强大的生物学活性。然而,缓激肽在生物流体中的半衰期极短,因此难以定量相关病理样本中释放的缓激肽量。因此,研究人员试图通过测量前体蛋白,如前激肽释放酶、激肽原和腺体激肽释放酶,来证明其参与情况或重要性。在这篇综述中,我想重点讨论对B/N Katholiek大鼠激肽释放酶-激肽系统的一项研究,该品系大鼠先天性缺乏血浆高分子量和低分子量激肽原。当将突变缺陷大鼠诱导的实验性炎症与正常大鼠(B/N-北里)诱导的炎症进行比较时,存在显著差异;即,缺陷大鼠在角叉菜胶诱导的爪肿胀中肿胀较小,在角叉菜胶诱导的大鼠胸膜炎中渗出物积聚较少。这些结果表明,缓激肽可能从激肽原释放,并且它可能在上述炎症中导致渗出物形成。此外,当通过DOCA-盐负荷诱导实验性高血压时,缺陷大鼠的血压比正常大鼠上升得更快。从上述发现可以得出结论,血浆激肽释放酶-激肽系统可能是身体防御机制如炎症和血压控制中的一个重要调节系统。

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