Wichmann M W, Angele M K, Ayala A, Cioffi W G, Chaudry I H
Center for Surgical Research, Brown University School of Medicine, Providence, Rhode Island, USA.
Shock. 1997 Oct;8(4):242-8.
Recent studies indicate beneficial effects of androgen depletion in male mice, before trauma-hemorrhage on cell-mediated immunity following soft-tissue trauma and hemorrhagic shock. Nonetheless, it remains unknown whether androgen receptor blockade following the insult has any salutary effects. To study this, male C3H/HeN mice were either sham-operated or subjected to soft-tissue trauma (i.e., 2.5 cm midline laparotomy) followed by hemorrhagic shock (blood pressure 35 +/- 5 mmHg for 90 min) and then adequately resuscitated (shed blood and lactated Ringer's). Immediately after the completion of resuscitation, as well as 24 and 48 h thereafter, the animals received either vehicle, 10 mg/kg body weight (BW) flutamide or 25 mg/kg BW flutamide subcutaneously. At 72 h after resuscitation, all animals were killed. The spleens and peritoneal macrophages (M phi) were then harvested and cultures established to determine IL-2 and IL-3 release, splenocyte proliferative capacity, as well as splenic and peritoneal M phi IL-1 release. Moreover, plasma testosterone and corticosterone levels were measured. Our results indicate that trauma-hemorrhage resulted in significant depression of splenocyte and M phi functions in vehicle-treated and animals receiving 10 mg/kg BW flutamide. Treatment with 25 mg/kg BW flutamide following trauma-hemorrhage, however, resulted in levels of cytokine release which were comparable with those found in sham-operated animals. No significant alterations in plasma corticosterone and testosterone levels were observed in any of the experimental groups. These findings indicate that short-term therapy of males with the androgen receptor blocker, flutamide at 25 mg/kg BW, following trauma-hemorrhage has protective effects on immune functions. This protective effect is dose dependent, since 10 mg/kg BW flutamide did not produce significant salutary effects. Thus, flutamide represents a novel and safe agent for improving the depressed functions in male trauma patients suffering severe blood loss.
最近的研究表明，在雄性小鼠遭受创伤性出血之前进行雄激素耗竭，对软组织创伤和失血性休克后的细胞介导免疫具有有益作用。然而，损伤后进行雄激素受体阻断是否有任何有益效果仍不清楚。为了研究这一点，对雄性C3H/HeN小鼠进行假手术或使其遭受软组织创伤（即2.5厘米中线剖腹术），随后进行失血性休克（血压35±5毫米汞柱，持续90分钟），然后进行充分复苏（回输 shed blood和乳酸林格氏液）。复苏完成后立即以及此后24小时和48小时，动物皮下注射载体、10毫克/千克体重的氟他胺或25毫克/千克体重的氟他胺。复苏后72小时，处死所有动物。然后采集脾脏和腹腔巨噬细胞（M phi）并建立培养物，以测定白细胞介素-2和白细胞介素-3的释放、脾细胞增殖能力以及脾脏和腹腔M phi白细胞介素-1的释放。此外，测量血浆睾酮和皮质酮水平。我们的结果表明，创伤性出血导致接受载体处理和接受10毫克/千克体重氟他胺的动物的脾细胞和M phi功能显著降低。然而，创伤性出血后用25毫克/千克体重的氟他胺治疗，导致细胞因子释放水平与假手术动物相当。在任何实验组中均未观察到血浆皮质酮和睾酮水平的显著变化。这些发现表明，创伤性出血后对雄性动物短期使用雄激素受体阻断剂氟他胺（25毫克/千克体重）对免疫功能具有保护作用。这种保护作用是剂量依赖性的，因为10毫克/千克体重的氟他胺没有产生显著的有益效果。因此，氟他胺是一种新型且安全的药物，可改善严重失血的男性创伤患者的功能抑制。
