Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine and Research Institute of Emergency Medicine, Hangzhou, Zhejiang 310009, China.
Chin Med J (Engl). 2010 Jul;123(13):1727-30.
The nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha (TNF-alpha) in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine.
Rat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-alpha were determined in every group.
The level of circulating TNF-alpha was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-alpha in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-alpha level at all the three tested doses. Galanthamine obviously decreased the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with vagotomy.
Cholinesterase inhibitor galanthamine has an inhibitory effect on TNF-alpha release in rats with lipopolysaccharide-induced peritonitis, and the vagus nerve plays a role in the process of the action of galanthamine.
神经系统通过迷走神经及其神经递质乙酰胆碱，可在体内下调全身炎症，最近有研究表明，脑胆碱能机制在激活这种胆碱能抗炎途径中起作用。加兰他敏是一种乙酰胆碱酯酶抑制剂，也是临床中可用的中枢作用胆碱能药物之一。本研究旨在评估加兰他敏对脂多糖诱导腹膜炎大鼠循环肿瘤坏死因子-α（TNF-α）的影响，以及迷走神经在加兰他敏作用中的可能作用。
建立大鼠脂多糖诱导腹膜炎模型和双侧颈迷走神经切断术。实验 1 中，大鼠随机分为对照组、腹膜炎组和腹膜炎组分别给予三种剂量的加兰他敏。实验 2 中，大鼠随机分为假手术组、假手术加腹膜炎组、假手术加腹膜炎组给予加兰他敏、迷走神经切断加腹膜炎组和迷走神经切断加腹膜炎组给予加兰他敏。检测各组大鼠血浆 TNF-α水平。
内毒素腹腔注射后大鼠循环 TNF-α水平明显升高。加兰他敏治疗可降低脂多糖诱导腹膜炎大鼠循环 TNF-α水平，与未治疗的脂多糖诱导腹膜炎大鼠相比差异有统计学意义。三种剂量中，3mg/kg 加兰他敏对循环 TNF-α水平的抑制作用最显著。加兰他敏明显降低假手术诱导腹膜炎大鼠的 TNF-α水平，但不能降低迷走神经切断诱导腹膜炎大鼠的 TNF-α水平。
乙酰胆碱酯酶抑制剂加兰他敏对脂多糖诱导腹膜炎大鼠 TNF-α释放有抑制作用，迷走神经在加兰他敏作用过程中起作用。
