CYTOKINE AND OPIATE REGULATE POSTOERATIVE BIOLOGICAL RESPONSE.

本项目的目的是确定脑室内注射TNF-α是否促进小鼠肠粘膜蛋白质合成速率的增加，2）脑中TNF-α的mRNA合成是否会根据剖腹手术伤口的长度而增加，3）静脉内施用纳洛酮是否阻断禁食大鼠肠粘膜的粘膜萎缩，（4）胆囊切除术后血浆吗啡水平是否升高;（5）侧脑室注射类固醇是否减少脑内TNF-α mRNA的合成，从而降低手术后的生物学反应。连续输注到脑室内空间导致肌肉蛋白质合成减少，但肠粘膜蛋白质合成增加，表明脑中的细胞因子与肠蛋白质周转有关，可能是由于TNF-α输注激活脑中的阿片系统。伤口长度越长，脑中的INF-α mRNA合成越多，表明伤口部位的疼痛刺激激活脑中的TNF-α合成，这导致尿中氮排泄的增加。给药纳洛酮可减轻禁食大鼠的肠道萎缩。禁食大鼠脑内吗啡水平升高，吗啡输注引起空肠粘膜萎缩。这些结果表明，阿片参与了肠上皮细胞的tumover。与禁食大鼠，开腹手术胆囊切除术后血浆中吗啡水平的提高，表明疼痛刺激增强细胞因子的mRNA合成和随后的吗啡在大脑中的生产。术前侧脑室注射类固醇阻断了脑内INF-α mRNA的合成，导致氮排泄减少。我们的结论是，脑内细胞因子和阿片类物质的调节降低了创伤后的生物反应。

The objectives of this project were to determine whether intracerebrobentricular injection of TNF-a facilitates an increase in protein synthesis rate of the gut mucosa in mice, 2) whether mRNA synthesis of TNF-a in the brain would be increased according to the length of wound for laparotomy, 3) whether intravenous administration of naloxone blocks mucosal atrophy of the gut mucosa in fasting rats, 4) whether laparotmy increases morphine levels in the plasma after cholecystectomy, and 5) whether intracerebroventiruclar injection of steroid would reduce mRNA synthesis of TNF-a in the brain, resulting in a reduction of biological response after laparotomy. A continuous infusion into the intracerebroventricular space caused a reduction of muscle protein synthesis but an increase in the gut mucosal protein synthesis, suggesting that cytokine in the brain is linked to the gut protein turnover probably due to activation of opiate system in the brain by TNF-a infusion. INF-a mRNA synthesis was increased in the brain by the longer length of wound, suggesting that pain stimuli from the wound site activate TNF-a synthesis in the brain, which causes an increase in nitrogen excretion in the urine. Administration of naloxone attenuated the atrophy of the gut in the fasting rats. Morphine levels in the brain were increased in fasting rats and morphie infusion caused the mucosal atrophy of the jejunum. These results indicated that opiate was involved in the enterocyte tumover. In association with fasting rats, open lapartomy enhanced morphine levels in the plasma after cholecystectomy, suggesting that pain stimuli enhanced mRNA synthesis of cytokine and subsequent production of morphine in the brain. Preoperative intracerebroventricular injection of steroid blocked synthesis of INF-a mRNA in the brain, resulting in a less nitrogen excretion. We concluded that regulation of cytokine and opiate in the brain reduced biological response after trauma.