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甘油诱导的急性肾衰竭对大鼠脾细胞谷胱甘肽状态及丝裂原诱导增殖的影响。

Effect of glycerol-induced acute renal failure on glutathione status and mitogen-induced proliferation of rat splenocytes.

作者信息

Yeung J H

机构信息

Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong.

出版信息

Methods Find Exp Clin Pharmacol. 1993 Sep;15(7):429-36.

PMID:8255121
Abstract

The mitogen-induced activation responses of rat splenic lymphocytes were determined for control and uremic rats. Lymphocyte activation was quantified by incorporation of [3H]thymidine. Glycerol-induced acute renal failure (ARF) inhibited the proliferation of both lipopolysaccharide (LPS)-induced B-lymphocytes and concanavalin A (Con A)-induced T-lymphocytes by 80% and 87%, respectively. The decrease in [3H]thymidine incorporation in both the LPS- and con A-activated cells significantly correlates with increases in plasma urea and creatinine concentrations (r = 0.83). Total glutathione (GSH) concentration in the splenocytes was not significantly different in terms of GSH per 10(7) cell, although the overall GSH and the number of viable splenocytes were generally lower in the uremic rats. Determination of GSH-related enzymes (GSH S-transferase, GSSG reductase and GSH peroxidase) in the spleen of control rats and rats with ARF showed little difference in the activities of these enzymes, although the GSSG/GSH ratio, which is an indication of oxidative stress, was significantly increased in the spleen of uremic rats. Incubation of normal splenocytes from control rats with uremic plasma obtained from rats with ARF also significantly decreased the proliferation responses. Metabolic inhibitors present in uremic plasma may contribute to the inhibitory action on mitogen-induced proliferation of B- and T-lymphocytes, although oxidative stress which occurs in ARF may itself be sufficient to affect the immune function.

摘要

测定了对照大鼠和尿毒症大鼠丝裂原诱导的脾淋巴细胞激活反应。通过[3H]胸腺嘧啶核苷掺入量来量化淋巴细胞激活。甘油诱导的急性肾衰竭(ARF)分别抑制脂多糖(LPS)诱导的B淋巴细胞和伴刀豆球蛋白A(Con A)诱导的T淋巴细胞增殖80%和87%。LPS激活细胞和Con A激活细胞中[3H]胸腺嘧啶核苷掺入量的减少与血浆尿素和肌酐浓度的增加显著相关(r = 0.83)。尽管尿毒症大鼠中总的谷胱甘肽(GSH)和活脾细胞数量通常较低,但每10(7)个细胞的GSH浓度在对照大鼠和尿毒症大鼠的脾细胞中并无显著差异。对照大鼠和ARF大鼠脾脏中GSH相关酶(GSH S-转移酶、谷胱甘肽二硫化物还原酶和GSH过氧化物酶)的测定显示,这些酶的活性差异不大,尽管作为氧化应激指标的谷胱甘肽二硫化物/谷胱甘肽(GSSG/GSH)比值在尿毒症大鼠脾脏中显著升高。用ARF大鼠的尿毒症血浆孵育对照大鼠的正常脾细胞也显著降低了增殖反应。尿毒症血浆中存在的代谢抑制剂可能对丝裂原诱导的B淋巴细胞和T淋巴细胞增殖有抑制作用,尽管ARF中发生的氧化应激本身可能足以影响免疫功能。

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