精氨酸加压素翻转脂多糖引起大鼠发热及其对痛觉敏感性的影响

目的:研究外周给精氨酸加压素(AVP)对脂多糖(LPS)引起的大鼠发热和痛觉过敏的影响,以及与血清中IL-1β和PGE_2水平变化的关系。方法:实验用成年雄性SD大鼠,在23℃环境温度下,明暗时间各12 h。用无线遥测系统连续测量大鼠体核温度(Tc)、棕色脂肪温度(T_(BAT))和活动。10:00或11:30分别给大鼠腹腔注射LPS(50μg/kg)、AVP(10μg/kg)或V1a受体阻断剂(30μg/kg)。用ELISA法测定血清IL-1β和PGE_2的含量。用足底痛觉测试仪(Hargreaves test)测试大鼠热痛缩爪潜伏期的变化。结果:(1)腹腔注射LPS引起大鼠双相发热过程伴有痛觉过敏现象。(2)AVP能够翻转LPS引起的Tc和T_(BAT)升高反应,降低发热引起的痛觉敏感性。(3)外周给V1a受体阻断剂能提高LPS引起的发热反应,但不影响发热引起的痛觉敏感性变化。(4)AVP能抑制LPS引起的发热大鼠血液中IL-1β和PGE_2水平升高。结论:(1)外周给予AVP可通过抑制棕色脂肪产热以及降低血液中IL-1β和PGE_2的浓度而翻转LPS发热反应并降低发热伴随的痛觉敏感性升高现象。(2)内源性AVP也有限制LPS发热的作用,但可能不影响发热引起的痛觉阈值降低现象。

Arginine vasopressin reverses fever induced by lipopolysaccharide in rats and its effect on hyperalgesia

AIM: To investigate the effect of peripheral administration of arginine vasopressin (AVP) on lipopolysaccharide (LPS)-induced fever and hyperalgesia in rats and its relationship with interleukine-1β (IL-1β) and prostaglandin E₂(PGE₂).METHODS: The core temperature (Tc), brown adipose tissue (BAT) temperature and activity were measured by telemetry in adult male Sprague-Dawley rats at an ambient temperature of 23 ℃ during a 12 h light/12 h dark photoperiod (lights on at 06:00 and lights off at 18:00). The rats were intraperitoneally injected with LPS (50 μg/kg), AVP (10 μg/kg) or V1a vasopressin receptor antagonist (V1a antagonist, 30 μg/kg) at 10:00 or 11:30. Hyperalgesia was assessed by measuring the latency to withdraw a hindpaw from radiant heat (Hargreaves test). The concentrations of IL-1β and PGE₂ in the serum were tested by ELISA. RESULTS: Intraperitoneal administration of LPS induced periods of biphasic fever accompanied by hyperalgesia. AVP reversed LPS-induced fever, and decreased the hyperalgesia and BAT thermogenesis. Peripheral administration of V1a antagonist enhanced the fever produced by LPS, but did not affect the hyperalgesia. AVP significantly attenuated LPS-induced IL-1β and PGE₂production. CONCLUSION: Peripheral administration of AVP reverses LPS-induced fever and decreases hyperalgesia by reduction of BAT thermogenesis and inhibition of IL-1β and PGE₂. Endogenous AVP attenuates the fever induced by LPS, but does not affect the nociceptive thresholds.