小胶质细胞在脂多糖引起的热高敏中的作用

目的探讨小胶质细胞在脂多糖引起的热高敏中的作用。方法清洁级雄性昆明小鼠,随机分成两组,每组5只,腹腔注射LPS组和注射PBS组,在注射前及后30、60、120、240 min测量小鼠足底的热痛阈;每组于注射前及后4h各处死5只取脑组织检测IL-1β、TNF-α;每组于腹腔注射4h时处死动物,免疫荧光确定脑组织中小胶质细胞的激活情况。然后分为四组,米诺环素+PBS组,米诺环素+LPS组,PBS+PBS组,PBS+LPS组,每组5只,连续三天腹腔注射米诺环素或PBS,第三天注射LPS或PBS,在注射前及后30、60、120、240 min测量小鼠足底的热痛阈;每组于注射前及后4h各处死5只取脑组织检测IL-1β、TNF-α。结果与注射PBS相比,注射LPS导致IL-1β、TNF-α分泌增加,注射60、120、240 min小鼠的热痛阈降低;与米诺环素+PBS组、米诺环素+LPS组、PBS+PBS组相比,PBS+LPS组导致IL-1β、TNF-α分泌增加,注射60、120、240 min小鼠的热痛阈降低。结论LPS激活小胶质细胞分泌促炎细胞因子导致热高敏。

Role of Microglia in Lipopolysaccharide-induced Thermal Hyperalgesia

Objective To explore the role of microglia in the lipopolysaccharide（LPS）-induced thermal hyperalgesia.Methods After adult kunming mice received an intraperitoneal injection of PBS or LPS,thermal nociceptive thresholds,IL-1β and TNF-α were determined;activation of microglia in the brain was determined by immunofluorescence.Then,according to the different agents,injected mice were divided into 4 groups： minocycline ＋ PBS,minocycline ＋ LPS,PBS ＋ PBS,and PBS ＋ LPS.The mice received an intraperitoneal injection of PBS or minocycline（the former agent of each group） for 3 consecutive days.On the 3 day,PBS or LPS（the latter agent of each group was added）.The thermal nociceptive thresholds and the expressions of brain IL-1β and TNF-α were assayed.Results LPS injection led to proinflammatory cytokine secretion and thermal hyperalgesia in kunming mice.Minocycline blocked LPS-stimulated inflammatory cytokine secretion and thermal hyperalgesia in kunming mice.Conclusion These data indicate that IL-1β and TNF-α are induced by LPS through activating brain-derived microglia,hence modulate thermal hyperalgesia.