Fecho K, Lysle D T
Department of Psychology and Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Cell Immunol. 2000 Jun 15;202(2):113-23. doi: 10.1006/cimm.2000.1653.
The present study assessed the effects of acute heroin treatment on the cellularity of the rat spleen and the rate of splenocyte death by necrosis or apoptosis. The results showed that 1 h after a single injection of heroin, the total number of leukocytes in the spleen was decreased in a dose-dependent manner. Prior injection of naltrexone completely blocked heroin's effect, and the heroin-induced decrease in splenic leukocytes was not associated with a heroin-induced increase in circulating leukocytes. A 1-h exposure to heroin did not increase levels of lactate dehydrogenase, a cytosolic enzyme, in supernatants of splenic mononuclear cells cultured for 45 min or 24 h, suggesting that heroin does not increase necrotic death in the spleen. In contrast, a 1-h heroin treatment did increase the percentage of Annexin V(+) cells in 0- and 24-h cultures of splenic mononuclear cells, indicating that heroin increases apoptotic death in the spleen. A 3-h exposure to heroin also produced a significant increase in apoptosis in the spleen. DNA fragmentation, a marker of cells in late stages of apoptosis, could not be detected in fresh splenocytes, but was evident in 24-h cultures of splenic mononuclear cells from saline- and heroin-treated rats. These results demonstrate that a single administration of heroin produces a decrease in the number of splenic leukocytes and an increase in the apoptotic death of splenic mononuclear cells.
本研究评估了急性海洛因处理对大鼠脾脏细胞数量以及脾细胞因坏死或凋亡而死亡的速率的影响。结果显示，单次注射海洛因1小时后，脾脏中白细胞的总数呈剂量依赖性减少。预先注射纳曲酮可完全阻断海洛因的作用，且海洛因引起的脾脏白细胞减少与循环白细胞增加无关。对脾单核细胞培养45分钟或24小时的上清液进行检测，结果表明，暴露于海洛因1小时并未使胞质酶乳酸脱氢酶水平升高，这表明海洛因不会增加脾脏中的坏死性死亡。相反，在脾单核细胞0小时和24小时培养中，1小时的海洛因处理确实增加了膜联蛋白V（+）细胞的百分比，表明海洛因会增加脾脏中的凋亡性死亡。暴露于海洛因3小时也会使脾脏中的凋亡显著增加。在新鲜脾细胞中未检测到DNA片段化（凋亡后期细胞的标志物），但在生理盐水处理组和海洛因处理组大鼠的脾单核细胞24小时培养中则很明显。这些结果表明，单次给予海洛因会导致脾脏白细胞数量减少以及脾单核细胞凋亡性死亡增加。
