Fuentes J M, Hanly E J, Aurora A R, De Maio A, Shih S P, Marohn M R, Talamini M A
Department of Surgery, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 665, Baltimore, MD, 21287-4665, USA.
Surg Endosc. 2006 Aug;20(8):1225-32. doi: 10.1007/s00464-005-0280-9. Epub 2006 Jul 24.
Laparoscopic surgery preserves the immune system and has anti-inflammatory properties. CO2 pneumoperitoneum attenuates lipopolysaccharide (LPS)-induced cytokine production and increases survival. We tested the hypothesis that CO2 pneumoperitoneum mediates its immunomodulatory properties via stimulation of the cholinergic pathway.
In the first experiment, rats (n = 68) received atropine 1 mg/kg or saline injection 10 min prior to LPS injection and were randomization into four 30-min treatment subgroups: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. In a second experiment, rats (n = 40) received atropine 2 mg/kg or saline 10 min prior to randomization into the same four subgroups described previously. In a third experiment, rats (n = 96) received atropine 2 mg/kg or saline 10 min prior to randomization into eight 30-min treatment subgroups followed by LPS injection: LPS only control; anesthesia control; and CO2 or helium pneumoperitoneum at 4, 8, and 12 mmHg. In a fourth experiment, rats (n = 58) were subjected to bilateral subdiaphragmatic truncal vagotomy or sham operation. Two weeks postoperatively, animals were randomized into four 30-min treatment subgroups followed by LPS injection: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. Blood samples were collected from all animals 1.5 h after LPS injection, and cytokine levels were determined by enzyme-linked immunosorbent assay.
Serum tumor necrosis factor-alpha (TNF-alpha) levels were consistently suppressed among the saline-CO2 pneumoperitoneum groups compared to saline-LPS only control groups (p < 0.05 for all four experiments). All chemically vagotomized animals had significantly reduced TNF-alpha levels compared to their saline-treated counterparts (p < 0.05 for all), except among the CO2 pneumoperitoneum-treated animals. Increasing insufflation pressure with helium eliminated differences (p < 0.05) in TNF-alpha production between saline- and atropine-treated groups but had no effect among CO2 pneumoperitoneum-treated animals. Finally, vagotomy (whether chemical or surgical) independently decreased LPS-stimulated TNF-alpha production in all four experiments.
CO2 pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway.
腹腔镜手术可保护免疫系统并具有抗炎特性。二氧化碳气腹可减弱脂多糖（LPS）诱导的细胞因子产生并提高生存率。我们检验了二氧化碳气腹通过刺激胆碱能途径介导其免疫调节特性的假说。
在第一个实验中，大鼠（n = 68）在注射LPS前10分钟接受1 mg/kg阿托品或生理盐水注射，并被随机分为四个30分钟的治疗亚组：仅LPS对照组、麻醉对照组、二氧化碳气腹组和氦气气腹组。在第二个实验中，大鼠（n = 40）在随机分组前10分钟接受2 mg/kg阿托品或生理盐水注射，随机分为上述相同的四个亚组。在第三个实验中，大鼠（n = 96）在随机分组前10分钟接受2 mg/kg阿托品或生理盐水注射，随机分为八个30分钟的治疗亚组，随后注射LPS：仅LPS对照组；麻醉对照组；以及4、8和12 mmHg的二氧化碳或氦气气腹组。在第四个实验中，大鼠（n = 58）接受双侧膈下迷走神经干切断术或假手术。术后两周，将动物随机分为四个30分钟的治疗亚组，随后注射LPS：仅LPS对照组、麻醉对照组、二氧化碳气腹组和氦气气腹组。在LPS注射后1.5小时从所有动物采集血样，通过酶联免疫吸附测定法测定细胞因子水平。
与仅生理盐水-LPS对照组相比，生理盐水-二氧化碳气腹组的血清肿瘤坏死因子-α（TNF-α）水平持续受到抑制（所有四个实验中p < 0.05）。除了二氧化碳气腹治疗的动物外，所有化学性迷走神经切断的动物与生理盐水处理的对应动物相比，TNF-α水平均显著降低（所有均p < 0.05）。用氦气增加气腹压力消除了生理盐水和阿托品处理组之间TNF-α产生的差异（p < 0.05），但对二氧化碳气腹处理的动物没有影响。最后，在所有四个实验中，迷走神经切断术（无论是化学性还是手术性）均独立降低了LPS刺激的TNF-α产生。
二氧化碳气腹独立于迷走神经和胆碱能途径调节免疫系统。
