蛋白酶在尿毒症分解代谢中作用的证据。

Evidence for the role of proteinases in uremic catabolism.

作者信息

Schaefer R M, Teschner M, Peter G, Leibold J, Kulzer P, Heidland A

机构信息

Department of Medicine, University of Wuerzburg, FRG.

出版信息

Adv Exp Med Biol. 1988;240:323-9. doi: 10.1007/978-1-4613-1057-0_38.

DOI:10.1007/978-1-4613-1057-0_38

PMID:3072849

Abstract

Enhanced muscle protein breakdown has been demonstrated in acutely uremic rats by numerous authors. In order to investigate the pathogenetic role of skeletal muscle proteinases leupeptin, a low-molecular weight proteinase inhibitor, was administered intraperitoneally to acutely uremic rats. Twenty-four hours after bilateral nephrectomy, leupeptin-treated animals displayed significantly lowered serum urea levels (-32%), as compared to untreated uremic rats. As a sign of muscle protein breakdown, plasma levels of Nt-methylhistidine, an indicator of myofibrillar protein degradation, were also decreased (-35%) in the uremic animals treated with leupeptin as compared to untreated uremic rats. Finally, leupeptin treatment resulted in a significant inhibition of the myofibrillar alkaline proteinase activity, a proteinase which has been related to various catabolic conditions. These findings suggest that the increased muscle protein breakdown in uremia is caused by enhanced activity of muscular proteinases and that anti-proteolytic agents display favourable effects on the enhanced protein degradation observed in acute uremia.

摘要

许多作者已在急性尿毒症大鼠中证实存在增强的肌肉蛋白分解。为了研究骨骼肌蛋白酶的致病作用，将一种低分子量蛋白酶抑制剂亮抑蛋白酶肽腹腔注射给急性尿毒症大鼠。双侧肾切除术后24小时，与未治疗的尿毒症大鼠相比，接受亮抑蛋白酶肽治疗的动物血清尿素水平显著降低（-32%）。作为肌肉蛋白分解的一个指标，与未治疗的尿毒症大鼠相比，接受亮抑蛋白酶肽治疗的尿毒症动物中，肌原纤维蛋白降解指标Nt-甲基组氨酸的血浆水平也降低了（-35%）。最后，亮抑蛋白酶肽治疗导致肌原纤维碱性蛋白酶活性受到显著抑制，这种蛋白酶与多种分解代谢状况有关。这些发现表明，尿毒症中肌肉蛋白分解增加是由肌肉蛋白酶活性增强所致，并且抗蛋白水解剂对急性尿毒症中观察到的蛋白降解增强显示出有利作用。