Sun X M, Dinsdale D, Snowden R T, Cohen G M, Skilleter D N
MRC Toxicology Unit, Carshalton, Surrey, U.K.
Biochem Pharmacol. 1992 Dec 1;44(11):2131-7. doi: 10.1016/0006-2952(92)90339-k.
The induction of apoptosis by glucocorticoids in isolated thymocytes has been studied extensively. However, it is not known whether or not the same changes occur after in vivo glucocorticoid treatment. In order to investigate this, we have studied the changes occurring in thymocytes isolated from rats, from 2-24 hr after a dose of dexamethasone (1 mg/kg), which caused 50% thymic atrophy. Thymocytes were separated into four fractions by isopycnic Percoll gradients. A loss of cells occurred within 2-8 hr, primarily in only one of the two major fractions of normal thymocytes. This loss of normal thymocytes coincided with the appearance of small dense cells with characteristic features of apoptosis including condensed chromatin, increased DNA fragmentation, internucleosomal DNA cleavage and a "hypodiploid" peak on flow cytometric analysis. Striking differences occurred in the cellular composition of the different Percoll fractions with time. Initially (up to 4 hr), the pattern of changes occurring in vivo resembled those found in vitro. However, at later times, the complex fate of apoptotic cells in vivo, such as phagocytosis, are not observed in the in vitro studies.
糖皮质激素诱导离体胸腺细胞凋亡的现象已得到广泛研究。然而，体内给予糖皮质激素后是否会发生同样的变化尚不清楚。为了探究这一问题，我们研究了从给予地塞米松（1毫克/千克）导致50%胸腺萎缩的大鼠体内分离出的胸腺细胞在2至24小时内发生的变化。胸腺细胞通过等密度Percoll梯度分离为四个组分。在2至8小时内细胞数量减少，主要发生在正常胸腺细胞的两个主要组分中的一个。正常胸腺细胞的这种减少与出现具有凋亡特征的小而致密的细胞同时发生，这些特征包括染色质浓缩、DNA片段化增加、核小体间DNA裂解以及流式细胞术分析中的“亚二倍体”峰。不同Percoll组分的细胞组成随时间发生显著差异。最初（直至4小时），体内发生的变化模式类似于体外观察到的情况。然而，在后期，体外研究中未观察到体内凋亡细胞的复杂命运，如吞噬作用。
