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糖皮质激素撤药对改善雌性糖尿病大鼠肝脏线粒体功能及酶活性的影响。

Effects of withdrawal of glucocorticoids on improving the function and enzymatic activities of liver mitochondria in female diabetic rats.

作者信息

Brignone J A, Campos de Brignone C M, Rebagliati de Mignone I R, Ricci C R, Susemihl M C, Rodríguez R R

机构信息

Departamento de Bioquímica, Facultad de Medicina, UBA, Argentina.

出版信息

Acta Physiol Pharmacol Ther Latinoam. 1991;41(3):309-23.

PMID:1668873
Abstract

In the present work the effects of corticosterone restitution were examined in female rats with chronic streptozotocin (SZ)-induced diabetes upon intact liver mitochondrial function and the activities of 3-hydroxybutyrate dehydrogenase (HBD), succinate dehydrogenase (SD) and cytochrome c oxidase (Cox) of the ruptured organelle. The liver mitochondrial function was analyzed by the respiration and the osmotic oscillatory behaviour. Respiration was measured by polarographic method and both the state 3 of active respiration (S3) and the respiratory control (RC) were determined using the following substrates: 3-hydroxybutyrate, succinate and malate-glutamate. The oscillatory behaviour was measured using as parameters the damping factors (DF) which are the ratios of amplitudes of two consecutive peaks or troughs of the spectrophotometrical tracings of this phenomenon. A group of control normal rats (N) and the following three groups of diabetic rats were studied: controls (D), adrenalectomized (D + ADX) and adrenalectomized with corticosterone restitution (D + ADX + C). The results of mitochondrial respiration showed that the mean values of S3 and RC decreased with the three substrates in the group D + ADX + C compared with D + ADX group (p < 0.001). This group demonstrated a significant increase of S3 and RC values of the respiration compared with the D group. The oscillatory behaviour of liver mitochondria of D + ADX + C group demonstrated a significant increase in the DF of peaks and troughs compared with D + ADX group. The values of DF of the latter group were not significantly different from the N group. The behaviour of the enzymes activities of ruptured liver mitochondria were different for each enzyme in the different groups of treated rats. Thus, in the D + ADX + C group the mean value of the activity of HBD significantly decreased, that of the Cox increased (p < 0.02) and that of SD did not show any variation compared with the corresponding values of the D + ADX group. Likewise, the mean value of HBD activity in this latter group was similar to that of the N group and that of Cox activity was lesser (p < 0.01) than that of the D group. The conclusion is drawn that corticosterone has significant additional diabetogenic effects upon biochemical functions of liver mitochondria in the SZ-induced diabetic state which could occur through the hormone cellular receptors.

摘要

在本研究中,我们检测了慢性链脲佐菌素(SZ)诱导的糖尿病雌性大鼠在给予皮质酮恢复处理后,其完整肝脏线粒体功能以及破碎细胞器中3-羟基丁酸脱氢酶(HBD)、琥珀酸脱氢酶(SD)和细胞色素c氧化酶(Cox)活性的变化。通过呼吸作用和渗透振荡行为分析肝脏线粒体功能。呼吸作用采用极谱法测量,使用以下底物测定活性呼吸状态3(S3)和呼吸控制(RC):3-羟基丁酸、琥珀酸和苹果酸-谷氨酸。振荡行为以阻尼因子(DF)为参数进行测量,DF是该现象分光光度记录中两个连续峰或谷的振幅之比。研究了一组对照正常大鼠(N)以及以下三组糖尿病大鼠:对照组(D)、肾上腺切除组(D + ADX)和肾上腺切除并给予皮质酮恢复处理组(D + ADX + C)。线粒体呼吸结果显示,与D + ADX组相比,D + ADX + C组使用三种底物时S3和RC的平均值均降低(p < 0.001)。与D组相比,该组呼吸作用的S3和RC值显著升高。D + ADX + C组肝脏线粒体的振荡行为显示,与D + ADX组相比,峰和谷的DF显著增加。后一组的DF值与N组无显著差异。在不同处理组大鼠中,破碎肝脏线粒体中各酶的活性表现各异。因此,与D + ADX组相应值相比,D + ADX + C组中HBD活性平均值显著降低,Cox活性升高(p < 0.02),SD活性无变化。同样,后一组中HBD活性平均值与N组相似,Cox活性比D组低(p < 0.01)。得出的结论是,在SZ诱导的糖尿病状态下,皮质酮对肝脏线粒体的生化功能具有显著的额外致糖尿病作用,这可能通过激素细胞受体发生。

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